Iron Metabolism and Absorption Quiz

Heavy Metal Poisoning (Iron)

• Heavy metal poisoning, specifically iron poisoning, is a serious health concern, especially in children under 6 years old, due to easily accessible iron preparations and their appeal.
• Accidental poisoning in adults is usually linked to suicide attempts.
• Iron ingestion amounts less than 20mg/kg of elemental iron typically cause no symptoms.
• Ingestion of 20 to 60mg/kg results in mild to moderate symptoms.
• Ingestion of more than 60mg/kg can lead to severe morbidity.

Learning Objectives

• Students will gain knowledge on the conditions that cause iron poisoning.
• Students will understand the pathophysiology behind iron toxicity.
• Students will be familiar with the clinical presentation of acute iron toxicity.
• Students will be familiar with the clinical presentation of chronic iron toxicity.
• Students will gain knowledge on the diagnosis and treatment of iron toxicity.

Circumstances of Poisoning

• Accidental poisoning in children under 6 years is common.
• Easily accessible iron preparations make accidental poisoning more likely.
• The appealing properties of iron preparations contribute to unintentional ingestion.
• Iron ingestion during pregnancy and postpartum is also frequent.
• Adult iron ingestions are usually associated with suicidal attempts.

Toxic Dose of Iron

• Ingestions of less than 20 mg/kg of elemental iron cause no symptoms
• Ingestions of 20 to 60 mg/kg result in moderate or mild symptoms.
• Ingestions of more than 60mg/kg can lead to significant morbidity

IRON Toxicokinetics

• Iron is absorbed more readily in its ferrous form (Fe2+) than its ferric form (Fe3+).
• Iron absorption occurs within the intestines.
• Iron is transported by a protein called transferrin within the bloodstream, usually within 300-500ug/dl (TIBC), with 50-150 ug/dl of normal serum iron.
• Citrate and ascorbate in citrus can increase iron absorption, while tannins in tea can decrease it.

Pathophysiology of Iron Toxicity

• Direct caustic injury to the gastrointestinal mucosa
• Impairment of cellular metabolism, mostly affecting the heart, liver, and central nervous system (CNS)
• Initial symptoms of vomiting, diarrhea, and abdominal pain due to the caustic effects of iron on the gut.
• Hemorrhagic necrosis of gastric or intestinal mucosa can lead to bleeding, perforation, and peritonitis.
• Unbound iron moves into cells and accumulates near mitochondrial cristae which results in uncoupling of oxidative phosphorylation and impairment of ATP synthesis.
• Cell membranes are damaged via free radical-mediated lipid peroxidation.
• Iron increases capillary permeability, inducing arteriolar and venodilation.
• Myocardial toxicity decreases cardiac output.
• The buildup of unbuffered protons worsens metabolic acidosis.
• Manifestations causing shock, cardiovascular collapse, and death.

Mechanism of Iron Toxicity

• Gastrointestinal tract (GIT) is a target organ in iron toxicity, with corrosive effects.
• Liver is a critical target. The portal vein carries iron to the liver where it causes immediate damage to hepatocytes, resulting in periportal injury and necrosis, followed by complete hepatic failure.
• Lipid peroxidation and the destruction of hepatic mitochondria contribute to liver damage.
• Metabolic acidosis is another crucial element.

Cardiovascular System

• Shock and vasodilation are caused by free circulating iron, damaging blood vessels and triggering histamine and serotonin release.
• Peripheral vasodilation contributes to venous pooling.
• Hepatic dysfunction causes coagulation defects.
• Iron inhibits clotting factors, increasing the risk of bleeding.
• Direct damage to the heart results in reduced myocardial contractility (negative inotropic effect).

Iron Poisoning- Symptoms

• Stages of iron poisoning are marked by specific symptom patterns.
• Symptoms can become serious as time progresses from Stage I-V.

Diagnosis of Iron Poisoning

• History of exposure to iron.
• Clinical findings such as hemorrhagic gastroenteritis, metabolic acidosis, and shock are crucial for diagnosis.
• Laboratory tests, including gastric fluid testing with H2O2 and deferoxamine, which can visually detect iron by creating a distinctive color change.
• Serum iron levels should be measured at their peak (3 to 5 hours) post-ingestion and at later intervals (6-8 hrs)
• Abdominal X-rays can reveal ingested iron tablets or diffuse densities/obstructions.
• Additional tests including liver function tests and acid-base assessment can provide additional information.

Treatment of Acute Iron Toxicity

• Prevention of further exposure is paramount
• Emergency and supportive care, including fluid resuscitation and management of metabolic acidosis, are crucial.
• Decontamination methods like whole-bowel irrigation with polyethylene glycol electrolyte lavage solution (PEG-ELS) is recommended for significant ingestions.
• Whole-bowel irrigation is done until the effluent is clear and there are no radiographic signs of pill fragments remaining in the gastrointestinal tract.
• PEG-ELS might be administered orally or via nasogastric tube.
• Whole-bowel irrigation is contraindicated in cases of bowel obstruction, perforation, or ileus.
• Enhanced elimination methods, such as hemodialysis and hemoperfusion, are typically ineffective.
• Exchange transfusions may be necessary for severely symptomatic patients with serum iron levels exceeding 1000 ug/dL.
• The use of deferoxamine mesylate as an antidote is a critical component in the treatment protocol.
• Deferoxamine mesylate is administered through intravenous infusion.
• Deferoxamine specifically targets non-transferrin-bound iron and aids in its excretion.

Chronic Iron Toxicity ("Hemosiderosis")

• Chronic iron toxicity arises from repeated blood transfusions or iron absorption disorders, leading to excess iron accumulation in the body's tissues.
• Ferritin, a protein that stores iron, increases dramatically in response to excess dietary iron.
• Iron accumulation in crucial organs like the heart, liver, spleen, and bone marrow leads to tissue destruction and dysfunction.
• Hemosiderin, another iron storage protein, usually results from cell damage and is often sequestered by macrophages.
• The build-up of iron leads to fibrotic changes and functional impairment in parenchymal tissues.