Iron poisoning (physical appearance, sources- dietary and environmental, uses- industrial and biological, usual fatal dose, toxicokinetics, mode of action, clinical features, diagnosis, treatment, autopsy features

1. PRESENTATION ON
IRON POISONING
PRESENTED BY:
SIDDIQUA PARVEEN
PHARM-D
SULTAN UL ULOOM COLLEGE
OF PHARMACY

2. IRON
PHYSICALAPPEARANCE
Metallic iron is silvery white in color, occurring naturally as
hematite, magnetite, etc. and usually causes no problems. In
fact it is an essential element and deficiency results in anemia.
Even if there is more than the required intake daily, the excess
is excreted. But in some individuals with inborn errors, even
normal dietary iron can cause toxic effects due to
accumulation, e.g. hemochromatosis (bronze diabetes).
Various iron salts are administered therapeutically in
individuals with iron deficiency anemia which can result from a
wide variety of causes. Iron poisoning is related in most
instances to overdose of such salts. One of the commonest is
ferrous sulfate (green vitriol) which occurs as bluish green
crystals. Iron (ferric) oxide, i.e. rust does not cause iron
poisoning.

3. HAEMATITE MAGNETITE
FERROUS SULPHATE

5. SOURCES
■ Dietary Sources:
The required daily amount of iron of 10–20
mg for adults is supplied through average
diet. The required intake increases to
25–30 mg in pregnancy. The average daily
intake for adults is 15 mg.
■ Environmental Sources:
Iron is found in 5.1% of the earth’s crust. It is
the second most abundant metal, and the
fourth most abundant element. It is believed
that the earth’s core consists mainly of iron.

6. USES:
Industrial uses
– Iron is primarily used in powder metallurgy and serves as a
catalyst in chemical reactions.
– Iron is a component of carbon steels, cast iron, high-speed steels,
high-strength low-alloy steels, manganese alloy steels, and
stainless steels.
– Steel is the most important alloy of iron. It contains 0.25–2% of
carbon.Alloyed with carbon (C), manganese (Mn), chromium (Cr),
nickel (Ni) and other elements, iron is used to form steel. – Wrought
iron is almost pure iron.
– Iron uses include magnets, dyes, pigments, and abrasives.
Biological uses
– Iron is essential to life. It is a constituent of biological pigments
such as hemoglobin, cytochromes and ferrichromes.

7. USUAL FATAL DOSE
The usual fatal dose corresponds to about 200 to 250
mg of elemental iron per kg of body weight. This can be
calculated from the percentage of elemental iron in a
particular preparation, e.g. a single 150 mg tablet of
anhydrous ferrous sulfate which contains 37% of
elemental iron will contain a total of 55 mg of elemental
iron. But such calculations can be misleading since
serious hepatotoxicity can result at much lower
concentrations of iron in the body which can lead to
death. In practice, this can be as low as 60 mg of
elemental iron/kg. Hence just a handful of these tablets
(15 to 20 in number), can be lethal to a young child.

8. TOXICOKINETICS
Iron poisoning occurs when serum iron level
exceeds the total iron-binding capacity
(TIBC), resulting in free circulating iron in the
bloodstream.
MODE OF ACTION
Free iron causes:
a. Massive post arteriolar dilatation which
results in venous pooling.
b. Increased capillary permeability resulting in
decreased plasma volume.

10. c. Oxidation of ferrous to ferric iron releasing
hydrogen ions. Subsequent hydration of ferric
iron results in metabolic acidosis.
d. Inhibits mitochondrial function leading to
hepatic damage, hypoglycaemia, and
hypoprothrombinaemia.
e. Inhibits thrombin-induced conversion of
fibrinogen into fibrin.
f. Has a direct corrosive action on the GI
mucosa.

11. CLINICAL FEATURES
Most cases occur in children. There are 5 stages:
■ Stage I (0.5 to 2 hours) includes vomiting,
hematemesis, abdominal pain, diarrhea,
haematochezia, lethargy, shock, acidosis, and
coagulopathy. Necrosis to the GI tract occurs from the
direct effect of iron on GI mucosa. Severe
gastrointestinal hemorrhagic necrosis with large losses
of fluid and blood contribute to shock. Free iron and
ferritin produce vasodilatation that may also contribute to
shock.
■ Stage II (after Stage I) includes apparent recovery and
may contribute to a false sense of security. Observe
closely.

12. ■ Stage III (2 to 12 hours after Stage I)
includes profound shock, severe acidosis,
cyanosis and fever. Increased total peripheral
resistance, decreased plasma volume,
haemoconcentration, decrease in total blood
volume, hypotension, CNS depression, and
metabolic acidosis have been reported.
■ Stage IV (2 to 4 days) includes possible
hepatotoxicity, convulsions, and coma.
Thought to be a direct action of iron on
mitochondria. Monitor liver function tests and
bilirubin. Acute lung injury may also occur.

13. The primary site of hepatic injury is the
periportal areas of the hepatic lobule (the
principal site for hepatic regeneration), which
may explain the increase in mortality and
poorer prognosis. Iron induced hepatotoxicity
is a presumed result of free radical
generation and lipid peroxidation. Iron
catalyzes hydroxyl radical formation (the
most potent-free radical), which initiates lipid
peroxidation. Based on limited data,
antioxidants may have a hepatoprotective
role in iron poisoning.

14. ■ Stage V (days to weeks) includes GI scarring
and strictures. GI obstruction secondary to
gastric or pyloric scarring may occur due to
corrosive effects of iron. Evaluate with barium
contrast studies. Sustained-release preparations
have resulted in small intestinal necrosis with
resultant scarring and obstruction. These stages
of iron poisoning may not occur in all patients.
After massive overdose, patients may present in
shock. With less serious overdoses, the initial
gastrointestinal symptoms may be the only
findings to develop even without treatment.

16. DIAGNOSIS
1. X-ray: Like all other heavy metals, iron and its
compounds are radiopaque. However, chewable iron
tablets and liquid iron formulations are usually not
visualized on x-ray. Completely dissolved iron
tablets/capsules may also not be radiopaque.
2. Serum iron level: Poisoning is indicated if this exceeds
150 mcg/100 ml, and serious toxicity is usually associated
with levels beyond 500 to 600 mcg/100 ml. Peak levels are
seen around 4 hours after ingestion. Measuring the total
iron binding capacity and relating it to the serum iron level is
often misleading and unreliable.
3. Total leucocyte count (TLC), electrolytes, glucose, blood
gas, clotting studies, liver function and renal function tests
are useful estimates.

18. 4. Chelation challenge test: Desferrioxamine in a dose of 25
mg/kg (maximum 1 gm.) is given IM. If the serum iron has
exceeded iron binding capacity, the excess iron is chelated
to desferrioxamine and the complex is excreted as a
pinkish (vin rosé) color in the urine. But a negative result
does not rule out iron poisoning.
5. Qualitative desferrioxamine color test (QDCT): 2 ml of
gastric fluid and 2 drops of 30% hydrogen peroxide are
placed in 2 plastic tubes. 0.5 ml of solution of
desferrioxamine (500 mg in 4 ml distilled water) is added
into one tube and the resulting color change is compared
with the other tube (control). If the test is positive, an orange
to red color will develop in the tube in which
desferrioxamine was added. The test must be done within
2 hours of ingestion of iron.

20. TREATMENT
1. Stomach wash with normal saline performed gently may
be of benefit in massive ingestions. Desferrioxamine must
not be used for lavage.
2.Activated charcoal is ineffective.
3. Magnesium hydroxide solution (1%) administered orally
may help reduce absorption of iron by precipitating the
formation of ferrous hydroxide. Magnesium hydroxide and
calcium carbonate containing antacids may safely be used
in therapeutic doses to help reduce iron absorption.
4. Obtain serum iron levels, creatinine, electrolytes, blood
haemoglobin concentration, blood prothrombin time,
baseline liver function tests, and arterial blood gases in
seriously poisoned patients.
5. Correction of hypovolaemia, and metabolic acidosis.

21. 6. Chelation therapy:
a. This is indicated in any of the following situations:
– More than one episode of vomiting or diarrhea.
– Significant abdominal pain, hypovolaemia, or acidosis.
– Multiple radiopacities on abdominal radiograph.
– Serum iron level greater than 350 mcg/100 ml.
b. Chelation can be done either with desferrioxamine
(parenteral) or deferiprone (oral).
– Dose (desferrioxamine):
- Intravenous Dose:Administer by continuous infusion at
a rate of up to 15 mg/kg/hr. Faster rates or IV boluses
may cause hypotension in some individuals. Infusion
rates up to 35 mg/ kg/hr have been used in children with
severe overdoses without adverse effects.

22. - Intramuscular Dose:Administer 90 mg/kg, up to a
maximum of 1 gm/dose, every 8 hours as needed. Pain
and induration at the injection site are often experienced.
- Total Daily Dose: The recommended total intravenous or
intramuscular daily dose should not generally exceed 6
grams.
Duration of Infusion: Duration of infusion is guided by the
patient’s clinical condition. Patients with moderate toxicity
are generally treated for 8 to 12 hours, those with severe
toxicity may require desferrioxamine for 24 hours or longer.
Patients should be re-evaluated for evidence of recurrent
toxicity (hypotension, metabolic acidosis) several hours
after the infusion is discontinued. Infusion duration of
greater than 24 hours has been associated with the
development of ARDS.

23. - Therapy Endpoint/Color Change: Monitor
urine for characteristic pink to orange-red
color (“vin rose”) indicating the excretion of
ferrioxamine (chelated iron) although
frequently a urine colour change is not seen.
In patients who demonstrate a color change,
desferrioxamine therapy may be discontinued
when the urine loses the “vin rose” color,
indicating a decrease in concentration of
chelated complex, if the patient is generally
asymptomatic.

24. – Adverse Effects:
- Sepsis
- Visual Toxicity (decreased visual acuity, night blindness,
color blindness, retinal pigmentary abnormalities).
- Ototoxicity
- Pulmonary Toxicity:A“pulmonary syndrome” has been
associated with high dose IV (10 to 25 mg/kg/hr)
desferrioxamine therapy for several days for acute and
chronic iron overload patients. Features include severe
tachypnoea, hypoxemia, fever, eosinophilia, preceding
urticaria, and pulmonary infiltrates.
- Hypotension
- Renal Toxicity: Elevated creatinine levels and decreased
creatinine clearances have been reported.

25. c. Continuous arteriovenous hemofiltration
(CAVH) may be helpful in severe poisoning.
d. Liver transplantation is the only therapeutic
avenue open in the presence of fulminant
hepatic failure.
AUTOPSY FEATURES
1. Hemorrhagic necrosis of gastric mucosa.
In ferrous sulfate poisoning, gastric contents
may appear bluish green in color.
2. Hepatic and renal necrosis.

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