Iron Toxicity

Normal iron content and storage

- About 70% of the iron in mammals is found in
hemoglobin, and about 5% to 10% is found in
myoglobin.

- When bound to normal hemoglobin and

myoglobin, iron is in the ferrous (Fe ) form.
2+

- Ferric iron is used in ironcontaining enzymes,

such as peroxidase, catalase, and cytochrome
oxidase
- Iron is transported & stored via iron binding
proteins hemosiderin, ferritin, and transferrin in
the liver, spleen, and bone marrow
Therapeutic uses
1-Pediatric or prenatal
vitamin
2-Treatment of Iron-
deficiency anemia
 Iron toxicity
Acute toxicity Chronic toxicity
- One of the leading Iron overload may develop
causes of death caused chronically in patients
by toxicological agents treated from chronic
in children younger than anemia or requiring
6 years. multiple transfusions of red
- Iron is particularly blood cells. This condition
tempting to young develops in patients with
children because it sickle cell disease,
appears similar to thalassemia leading to
candy. Hemochromatosis
 Toxic Doses
[>20 mg/kg] signs of GI toxicity

[ > 40 mg/kg] Moderate-to-severe

intoxication

[ >60 mg/kg] lethal

Pathophsiology
Corrosive
toxicity
Metabolic
acidosis
Cellular
toxicity
 Pathophsiology
Corrosive toxicity
Iron is an extremely corrosive
substance to the GIT mucosal
tissues

Nausea, Hematemesis & Diarrhea

may progress to life threatening
hemorrhagic gastritis, perforation,
and peritonitis

Hypovolemia & Hypoperfusion

Metabolic acidosis
 Pathophsiology
Cellular toxicity
Absorption of excessive iron
(In overdose the corrosive effect
facilitate iron absorption)
Iron-binding proteins become
saturated, free iron ions are
allowed into the general circulation
(Systemic iron toxicity)
Iron penetrates the cells of the
liver, heart, and brain leading
to oxidative stress

Metabolic acidosis???
 Pathophsiology
Cellular toxicity
Generation of free radicals &H+ ions via
Fentons reaction

(1) Fe2+ + H2O2 Fe3+ + OH (hydroxyl radical) + OH

(2) Fe3+ + H2O2 Fe2+ + OOH (peroxide radical) + H+

 Pathophsiology
Cellular toxicity

Excessive free radicals

Production

Impaired oxidative
Phosphorylation &
mitochondrial dysfunction

Anaerobic metabolism
& lactic acid production

Metabolic
acidosis
 Clinical presentation
Iron poisoning is often classified into 5 distinct
stages
Stage 1 [the gastrointestinal (GI)
phase ]
30m to 6 hrs

Stage 2 [Latent phase]

2 to 4 hrs

Stage 3 [metabolic/CVS]
2 to 24 hrs

Stage 4 [Hepatic]
12 to 24 hrs

Stage 5 [delayed ]
1 to 7 weeks
Stage 1 [the gastrointestinal (GI) phase ]

Nausea, abdominal pain, vomiting & diarrhea

In severe intoxication, a hemorrhagic component
is observed in conjunction
with gastroenteritis
The combination of fluid and blood loss,
may result in hypovolemia or shock
Fatal in significant% of cases
 Stage 2 [Latent phase]

Resolution of GI symptoms (Apparent clinical

improvement)
Occurs 6-12 hrs postingestion & may last up to 24
hrs
Metabolic abnormalities begin to evolve
 Stage 3 [metabolic/CVS]
Metabolic acidosis & CVS symptoms
Also characteristic of CNS symptoms, usually
seziures and coma.
Shock & multiorgan failure can occur; acute renal
failure & severe pulmonary edema
Most patients die during this phase.
It can start very early (6-8 h), depending on
severity of exposure, and it can last up to 2 days
 Stage 4 [Hepatic]
Hepatic dysfunction (necrosis) (Elevated liver
enzymes, bilirubin)
Hypoglycemia may accompany liver
dysfunction.
Impaired coagulation (hemorrhage) due to
hypoprothrombinemia
Hepatic encephalopathy (hyperammonemia) /
coma
 Stage 5 [Delayed]

Scarring of the healing GI tract

The stomach and/or intestines may be affected,
resulting in gastric outlet or intestinal obstruction
Experienced weeks after a severe poisoning
 Treatment
1- ABCD
Hypovolemia: IV 0.9% isotonic sodium chloride &
vasopressors for hypotension

2- Prevent further absorption from the gut

Adsorption to activated charcoal is minimal
Whole bowel irrigation is the GI decontamination
method of choice using PEG administered via NG or OG
tube until rectal effluent is clear

[MOA: Laxative with strong electrolytic and osmotic

effects that has cathartic actions in the GI tract.], [CI in
GI obstruction]
 Treatment
3- Supportive& symptomatic treatment
*IV NaHCO3 for acidosis

4- Specific Antidote [Chelating Agent]

Serum iron Serum iron

levels >350 g/dL levels >500 g/dL
with evidence of regardless of
toxicity signs or
(Symptoms) symptoms
 Deferoxamine
- Administer by IV infusion until serum iron level:
drops to <350 g/ dL or until resolution of clinical
symptoms
- 8 mg of iron is bound by 100 mg of deferoxamine
The complex is water soluble and excreted in urine
giving urine a red discoloration (Vin-ros urine)

Contraindications
Known sensitivity to desferrioxamine, Use with
caution in patients with renal impairment
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