Gastrointestinal Symptoms and Poisoning Quiz

Heavy Metals Poisoning (Iron)

• Iron poisoning is a common and serious accidental poisoning, especially in children under 6 years old.
• Many iron preparations are easily accessible and attractive to children.
• Iron ingestion is frequently seen during pregnancy and the postpartum period.
• In adults, serious iron ingestion is often associated with suicidal attempts.

Learning Objectives

• Circumstances and toxic dose of iron poisoning
• Pathophysiology and mechanism of iron toxicity
• Clinical presentation of acute iron toxicity
• Clinical presentation of chronic iron toxicity
• Diagnosis and treatment of iron toxicity

Circumstances of Poisoning

• Accidental poisoning is common and serious in children under 6 years due to easily accessible and attractive preparations.
• This is also a concern during pregnancy and postpartum periods.
• In adults, iron ingestion is frequently associated with suicidal attempts.

Toxic Dose of Iron

• Ingestion of less than 20 mg/kg of elemental iron usually causes no symptoms.
• Ingestion of 20 to 60 mg/kg results in mild to moderate symptoms.
• Ingestion of more than 60 mg/kg can lead to severe morbidity.

Iron Toxicokinetics

• Absorption: Ferrous iron (Fe+2) is more readily absorbed than ferric iron (Fe+3).
• Distribution: Iron is transported in the blood bound to a protein called transferrin. Total iron-binding capacity (TIBC) is usually 300–500 ug/dL and normal serum iron level is 50–150 ug/dL. There is usually no free iron circulating in the blood. Citrate and ascorbate in citrus fruits can increase iron absorption, while tannins in tea can decrease absorption.

Pathophysiology of Iron Toxicity

• Two distinct toxic effects:
  • Direct caustic injury to the gastrointestinal mucosa.
  • Cellular metabolism impairment, primarily affecting the heart, liver, and central nervous system.
• Caustic effects on the gut lead to vomiting, diarrhea, and abdominal pain.
• Hemorrhagic necrosis of the gastric or intestinal mucosa can cause bleeding, perforation, and peritonitis.
• Unbound iron moves into cells, localizes near the mitochondrial cristae, resulting in uncoupling and impairment of adenosine triphosphate (ATP) synthesis.
• Cell membranes are damaged by free radical-mediated lipid peroxidation.
• Iron increases capillary permeability and induces arteriolar and venodilation.
• Myocardial toxicity decreases cardiac output.
• Hypoperfusion and hydration result in excess unbuffered protons, worsening metabolic acidosis.
• Gastric/intestinal fluid losses, combined with other effects, can lead to shock, cardiovascular collapse, and death.

Mechanism of Iron Toxicity

• Systems Affected: Gastrointestinal (GIT) - potent corrosive effect. Liver – the portal vein transports iron directly to the liver. Iron contacts hepatocytes and causes immediate, periportal injury, necrosis and complete hepatic failure. Lipid peroxidation & destruction of hepatic mitochondria occur.
• Metabolic acidosis is another effect.

Cardiovascular System

• Shock is caused by vasodilation due to free circulating iron. Damage to blood vessels (BV) releases histamine and serotonin, causing peripheral vasodilation leading to venous pooling. Coagulation defects are caused by hepatic dysfunction and iron inhibits clotting factors (inhibiting thrombin). Free iron also damages the heart, reducing myocardial contractility (negative inotropic effect).

Symptoms of Iron Poisoning

• Stage 1: 0.5–2 hours: nausea, vomiting, hematemesis, abdominal pain, diarrhea, shock, and coagulopathy.
• Stage 2: 2–12 hours: profound shock, severe acidosis, convulsions, coma, and acute lung injury.
• Stage 3: 12–24 hours: Multisystem organ failure and/or shock, severe GI hemorrhage, coma, renal insufficiency, jaundice, coagulation defects, progressive pulmonary dysfunction, pancreatic and hepatic injury leading to hyperglycemia.
• Stage 4: Weeks (later sequelae): liver cirrhosis, gastric scarring, pyloric stricture.

Treatment of Acute Iron Toxicity

• Prevent further exposure and emergency supportive treatment
• Decontamination: Syrup of ipecac is not recommended due to its adverse effects; gastric lavage is unlikely to be useful; whole-bowel irrigation with polyethylene glycol electrolyte lavage solution (PEG-ELS) is recommended for significant ingestions.
• Enhance elimination: Hemodialysis and hemoperfusion are ineffective to remove iron due to its large distribution volume. For patients with serum iron levels exceeding 1000 µg/dL, exchange transfusions have been recommended.
• Specific antidote: Deferoxamine mesylate (Desferal) is a specific antidote.

Diagnosis of Iron Poisoning

• History of exposure: Identification and time of exposure to iron
• Clinical picture: include hemorrhagic gastroenteritis, metabolic acidosis, shock
• Investigations:
  • Laboratory findings (Serum/iron levels, Gastric fluid + H₂O₂ + deferoxamine tests for detection of ferrioxamine)
  • Abdominal radiographs: identification of tablet/diffuse densities.

Chronic Iron Toxicity ("Hemosiderosis")

• Mechanism: When excess dietary iron is absorbed, the body produces more ferritin, which is highly abundant in the heart, liver, spleen, and bone marrow. However, iron causes tissue destruction in these organs. Iron overload is characterized by increased levels of ferritin and hemosiderin (another storage protein, a result of cellular damage, engulfed by macrophages).
• Causes: Repeated blood transfusions in conditions like thalassemia major or sickle cell disease, or rarely due to a defect in iron storage proteins causing excessive iron absorption.
• Effects: Iron deposition in parenchymal tissues, leading to fibrotic changes and functional impairment.

Additional Information

• Normal serum iron levels range from 50-150 µg/dL.
• Serum iron levels measured at peak (3-5 hours after ingestion) is the most useful test to evaluate severity. 50-175 µg/dL- normal or mild toxicity, 350-500 µg/dL- mild to moderate toxicity; > 500 µg/dL (Hepatotoxicity), 500-1000 µg/dL (Shock & systemic toxicity), >1000 µg/dL (fatal).
• Sustained-release or enteric-coated preparations may have erratic absorption, requiring a second serum iron level test (6-8 hours after ingestion).