Iron Toxicity😍

Iron Toxicity

Definition & Overview

• Harmful effects from excessive iron.

• Can be acute (e.g., overdose) or chronic (e.g., iron overload).

• A metal storage disease.

Etiology

• Acute: 
• Iron supplement ingestion (accidental/intentional).

• Chronic:
• Primary (Hereditary Hemochromatosis):
• HFE gene mutation (C282Y) → ↓↓ hepcidin → ↑ iron absorption.
• Secondary:
• Chronic blood transfusions (e.g., thalassemia, SCA).

Pathogenesis

• Excess iron → ROS (Fenton) → oxidative stress, cell damage.

• Iron accumulates as hemosiderin
• Causes organ damage

Acute Iron Toxicity

Clinical Presentation

• Onset: 30 minutes to 6 hours post-ingestion.

• Lethal Dose:
• Approximately 20-60 mg/kg elemental iron.
• >60 mg/kg is life-threatening.

Stages of Acute Toxicity:

Diagnosis

• History & symptoms.

• Laboratory:
• Serum iron levels:
• >500 µg/dL indicates severe toxicity.
• TIBC:
• Low or saturated.
• HAGMA, elevated glucose, leukocytosis.
• ↑↑ liver enzymes.
• Coagulopathy in severe cases.

• Abdominal X-ray
• Radiopaque iron tablets.

Treatment

• Emergency Management:
• Airway, breathing, circulation
• Gastric decontamination:
• Whole bowel irrigation if tablets visible on X-ray.
• Avoid induced vomiting or lavage due to perforation risk.

• Chelation Therapy

Fe chelating agents

Chronic Iron Toxicity

• Presents after age 40.

• Slower progression in females due to iron loss from menstruation.

• Classic Triad:
• Cirrhosis
• Diabetes mellitus (“bronze diabetes”)
• Affects insulin production
• Skin pigmentation (bronze or grey)
• Due to melanin

Symptoms by Organ System:

Laboratory Findings:

Imaging/Biopsy:

• Detects hemosiderin deposits
• Gold standard
• Via
• Liver MRI (T2 or FerriScan) /
• Biopsy with Prussian blue stain

• Cardiac T2 MRI
• Assesses heart iron levels in transfusion-dependent patients

• Liver MRI
• Appears Jet black

Genetic Testing in Hemochromatosis:

• C282Y mutation in HFE gene → chromosome 6

Treatment

• Iron Chelation Therapy:
• For Secondary Iron Overload → Transfusion-Related
• Indicated in severe iron overload
• Start Early Chelation if: 
• Transfusions > 10–20
• Ferritin > 1000 µg/L

• Chelating Agents:
• Desferrioxamine/Deferoxamine
• Injectable
• DOC for acute Iron poisoning
• When Iron level > 500 Microgram/dl
• Monitor for hypotension, pulmonary toxicity.
• Oxygen → acute → IV → but BP falls and Lung injury
• Deferiprone
• Oral
• Used for chronic Iron overload
• Agranulocytosis
• needs weekly blood monitoring
• Best for cardiac iron;
• Chronic Ferry Pirates (Feripirone) → oral
• Prone (Deferiprone) Close (Clozapine) Car (Carbamazepine) → Agranulocytosis

Monitoring

• Regular monitoring of:
• Ferritin
• Transferrin saturation
• MRI (liver and cardiac).

• Adjust chelation based on iron burden.

Supportive Measures

• Avoid:
• Iron-rich foods.
• Iron supplements.
• Excessive alcohol (increases HCC risk).

• Vitamin C:
• In moderation only.
• Helps iron excretion.
• Excess may raise free iron levels.

Hemochromatosis

DCM > RCM

Genetic Factors:

• Associated with HFE gene (on chromosome 6) → C282Y mutation → ↓ Hepcidin

• HJV gene (hemojuvelin for juvenile hemochromatosis)

Imaging/Biopsy:

• Detects hemosiderin deposits
• Gold standard
• Via
• Liver MRI (T2 or FerriScan) /
• Biopsy with Prussian blue stain

• Cardiac T2 MRI
• Assesses heart iron levels in transfusion-dependent patients

• Liver MRI
• Appears Jet black

Genetic Testing in Hemochromatosis:

• C282Y mutation in HFE gene → chromosome 6

Hemochromatosis Treatment:

• Repeated phlebotomy.
• Remove 500 mL blood weekly.
• Continue till:
• Ferritin <50 µg/L.
• Transferrin saturation <50%.
• Maintenance:
• Every 2–3 months..
• Improvements seen
• ↓ Liver size, ↑ Hepatic function, ↓ Skin pigmentation, Reversal of cardiac dysfunction, Better glycemic control
• Poor / No response
• Arthropathy, Hypogonadism

• Drug of choice:
• Iron chelators (e.g., deferoxamine, deferiprone).
• Desferrioxamine/Deferoxamine
• Injectable
• DOC for acute Iron poisoning
• When Iron level > 500 Microgram/dl
• Monitor for hypotension, pulmonary toxicity.
• Oxygen → acute → IV → but BP falls and Lung injury
• Deferiprone
• Oral
• Used for chronic Iron overload
• Agranulocytosis
• needs weekly blood monitoring
• Best for cardiac iron;
• Chronic Ferry Pirates (Feripirone) → oral
• Prone (Deferiprone) Close (Clozapine) Car (Carbamazepine) → Agranulocytosis