Iron poisoning typically occurs from ingestion of excess iron that results in

acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

. Mild symptoms which occur within hours include

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

, and

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

. In more severe cases, symptoms can include

tachypnea Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing. In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s, or

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

. If left untreated, iron poisoning can lead to multi-organ failure resulting in permanent organ damage or death.

Iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

is available over the counter as a single entity supplement in an iron salt form or in combination with vitamin supplements and is commonly used in the treatment of

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

Overdoses A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

on iron can be categorized as unintentional ingestion which is predominantly associated with children or intentional ingestion involving suicide attempts in adults. Unintentional ingestion of iron containing drug products are a major cause of mortality in children under the age of 6 years old in the United States. As a response, in 1997 the US Food and Drug Administration (FDA) implemented a regulation requiring warning labels and unit dose packaging for products containing more than 30 mg of elemental iron per dose. The diagnosis of iron poisoning is based on clinical presentation including laboratory tests for serum iron concentrations and

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...

along with physical examination. Treatment for iron poisoning involves providing

fluid replacement Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous ...

, gastrointestinal decontamination, administering

deferoxamine Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an ...

intravenously, liver transplants, and monitoring the patient's condition. The degree of intervention required depends on whether the patient is at risk for serious toxicity.

Signs and symptoms

Manifestation of iron poisoning may vary depending on the amount of iron ingested by the individual and is further classified by five stages based on timing of signs and symptoms. In mild to moderate cases, individuals may be

asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered a ...

or only experience mild gastrointestinal symptoms that resolve within six hours. In serious cases, individuals may present with systemic signs and symptoms and require treatment. Clinical presentation of iron poisoning in the absence of treatment progresses in five stages: the gastrointestinal phase, latent phase,

and shock phase,

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

phase, and

bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs ...

due to scarring. The first indication of iron poisoning occurs within the first six hours post-ingestion and involves gastrointestinal symptoms including abdominal pain accompanied by nausea and vomiting with or without blood. Due to the disintegration of iron tablets, the stool may appear as black or dark green or gray. After the first stage, gastrointestinal symptoms appear to resolve in the latent phase and individuals may show signs of improvement. Following this stage, the iron begins to affect the cells of the body's organs which manifests as numerous systemic signs and symptoms developing after 6 to 72 hours, in the metabolic acidosis phase. Individuals may present with signs of

cardiogenic shock Cardiogenic shock (CS) is a medical emergency resulting from inadequate blood flow due to the dysfunction of the ventricles of the heart.Textbooks of Internal MedicinHarrison's Principles of Internal Medicine 16th Edition, The McGraw-Hill Compan ...

indicated by low blood pressure, rapid heart rate and severe shortness of breath. Hypovolemic shock occurs due to loss of blood from the gastrointestinal bleeding caused by the iron. During this phase,

may also develop damaging internal organs such as the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

and

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

. In the fourth stage taking place 12 to 96 hours after ingestion, liver toxicity and failure occurs as the cells begin to die. In the last stage of iron poisoning following 2 to 8 weeks after ingestion, scarring of the gastrointestinal mucosal lining resulting in bowel obstruction.

Cause

Pathophysiology

Iron is essential for the production of

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...

in red blood cells which is responsible for transporting oxygen throughout the body. In normal physiologic conditions, nonionic forms of iron (Fe°) are converted into

ferrous iron In chemistry, iron(II) refers to the element iron in its +2 oxidation state. In ionic compounds (salts), such an atom may occur as a separate cation (positive ion) denoted by Fe2+. The adjective ferrous or the prefix ferro- is often used to sp ...

(Fe²⁺) by gastric acid in the stomach. Ferrous iron is then absorbed in the small intestine where it is oxidized into its ferric iron (Fe³⁺) form before being released into the bloodstream. Free iron in the blood is toxic to the body as it disrupts normal cell function, damaging organs such as the liver, stomach, and cardiovascular system. The human body has protective mechanisms in place to prevent excess free ferric iron from circulating the body. When being transported throughout the body, iron is bound to an iron transporting protein called

transferrin Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encod ...

to prevent iron from being absorbed into different cells. Any excess iron is stored as

ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ...

in the liver. In the event of iron overdose, iron stores become oversaturated and the body's protective mechanisms fail resulting in excess free circulating iron.

Toxic Dose

Iron poisoning can occur when doses of 20 to 60 mg/kg or more of elemental iron is ingested with most cases reporting primarily gastrointestinal symptoms. Systemic signs and symptoms shown in serious toxicity occur at higher doses exceeding 60 mg/kg. Ingesting above 120 mg/kg may be fatal. The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Individuals who have ingested less than 20 mg/kg of elemental iron typically do not exhibit symptoms. It is unlikely to get iron poisoning from diet alone with iron supplements being the cause of overdose. The amount of elemental iron in an iron supplement can be calculate based on the percentage it constitutes for per tablet. For example, a 300 mg tablet of ferrous fumarate will contain 100 mg of elemental iron or 33%. * Ferrous sulfate contains 20% elemental iron per mg of mineral salt * Ferrous gluconate contains 12% elemental iron per mg of mineral salt * Ferrous fumarate contains 33% elemental iron per mg of mineral salt

Diagnosis

Iron toxicity is primarily a clinical diagnosis that involves getting a detailed patient history and physical examination of the individuals signs and symptoms. Information such as how much iron was ingested and the timing should be gathered to assess the level of toxicity. Signs for severe iron poisoning should be evaluated such as any confusion or extreme

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

, increased heart rates, low blood pressure for adults. In children, signs of shock can be noted with behavioral changes such as decreased responsiveness, crying, and inability to focus. Persistent vomiting is often associated with iron poisoning and also used to determine severity of iron poisoning. Laboratory tests such as measuring the peak serum iron level after 4 to 6 hours of ingestion can be useful in determining the severity of iron toxicity. In general, levels below 350mcg/dL are associated with more mild iron poisoning while upper levels above 500mcg/dL are associated with more severe iron poisoning. Measuring electrolyte levels, kidney function,

serum glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the bl ...

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

(enzymes and

bilirubin Bilirubin (BR) ( Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from t ...

complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and ...

, clotting time via prothrombin and partial thromboplastin time, anion gap for metabolic acidosis, should be conducted for clinical monitoring and confirmation of iron poisoning. The deferoxamine challenge test is a diagnostic test for confirming iron poisoning, however it is no longer recommended for diagnostic purposes due to concerns regarding the accuracy.

Deferoxamine Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an ...

can be administered intramuscularly as a single dose where it then binds to free iron in the blood and is excreted into the urine turning it to a "brick orange" or pink/red/orange color.

Radiographs Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeut ...

are no longer used for diagnosis due to the lack of connection between severity of iron toxicity and the presence of radiopaque iron tablets in the stomach on X-rays. This method also requires that the ingested tablet to be radiopaque which most iron preparations are not.

Treatment

Management of acute iron poisoning involves providing a patient with respiratory support and

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

deferoxamine. Patients exhibiting severe symptoms in the gastrointestinal phase should receive volume resuscitation to prevent hypovolemic shock from the loss of blood volume. Normal saline is administered intravenously to maintain adequate volume of fluid in the body. Deferoxamine is a drug that is used in cases of serious iron poisoning. It is a

chelating agent Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands a ...

and binds to free iron in the body in order to be eliminated by the kidneys into urine. Dosing of deferoxamine should be determined through consultation with a toxicologist but is typically continuously infused at 15 mg/kg to 35 mg/kg per hour and not exceeding the maximum daily dose of 6 grams for adults. In pediatric patients, doses should not exceed 15 mg/kg per hour. recommended duration of treatment is until symptoms have resolved which is usually 24 hours. In non-fatal cases of iron poisoning where there is liver failure, liver transplantation may be necessary. Treatment of iron poisoning should be based on clinical presentation, peak serum iron levels and other laboratory results. As a general guideline, patients who have ingested lower doses of elemental iron, have a peak serum iron level less than 500mcg/dL and are asymptomatic or only exhibit mild gastrointestinal symptoms typically do not require treatment and should be monitored for 6 hours after ingestion. In cases where high doses of elemental iron have been ingested and the patient is exhibiting signs and symptoms of severe systemic iron poisoning, supportive care measures like volume resuscitation and deferoxamine should be initiated immediately. A quick response to iron poisoning can significantly improve clinical outcomes.

References

External links

Iron poisoning
in General Practice Notebook
Iron Poisoning
at WebMD

Merck Manual ''The Merck Manual of Diagnosis and Therapy'', referred to as ''The Merck Manual'', is the world's best-selling medical textbook, and the oldest continuously published English language medical textbook. First published in 1899, the current print e ...

{{Elements in biology

Poisoning A poison can be any substance that is harmful to the body. It can be swallowed, inhaled, injected or absorbed through the skin. Poisoning is the harmful effect that occurs when too much of that substance has been taken. Poisoning is not to ...

Toxic effects of metals