Iron Toxicity: Onset and Emergency Treatment

Iron is a naturally occurring element found in great abundance throughout the universe. It is the chemical that gives red clay and the planet Mars their characteristic color; and it is found in products from paper clips to engine blocks. Iron is the essential chemical component of steel, and of course it is a mineral that is essential to life. As with all mineral nutrients, too little iron can be detrimental to one's health. Unlike many other essential minerals however, an excess of iron can result in illness and even death. Although death resulting from an iron overdose is rare, most victims of this avoidable tragedy are children aged five or under.1 This statistic, combined with the fact that the bodily absorption and metabolism of iron is affected by some very common behaviors in our society, makes the course and causes of iron toxicity pertinent knowledge for health care providers of every level.

This article addresses three topics regarding iron as a nutritional chemical: the role of iron in normal human physiology, the onset and presentation of iron toxicity, and the emergency treatment of patients suffering from iron overdose.

The Role of Iron

There are two classes of nutritional minerals: macro minerals, which the body requires in relatively large amounts, and trace minerals, which are only needed by the body in very small amounts. Iron is a trace mineral that aids in cell growth and division2. It is also the inorganic molecule upon which the oxygen-bearing proteins hemoglobin and myoglobin are formed.3

Iron is present in a variety of foods, but only a small percentage of iron that is ingested is absorbed in the gut.4 Iron that comes from animal products (called heme iron) is more easily absorbed by the body than iron found in non-animal foods. Absorption also depends on the level of iron stores in the body, as well as the presence of chemicals such as copper, cobalt, and manganese, which expedite the absorption of iron. Vitamin C is of particular benefit for those who suffer from insufficient iron stores for it greatly aids in iron absorption. Foods high in Vitamin C include citrus fruits, green peppers, broccoli, strawberries and cabbage.8 It is important to understand however, that rapid absorption of iron does not necessarily equate to its being beneficial to one's health. For example, iron that is dissolved in liquid is absorbed very easily and quickly enters the bloodstream; this "liquid" iron is also very corrosive and can damage the gastrointestinal tract.7

While some substances aid absorption of iron in the gut, others inhibit its absorption. Phytic acid is an organic molecule found in whole grains and legumes that has recently been shown to have some positive benefits for lab rats. However, phytic acid has long been known to bind proteins, starches, and minerals such as iron and slow their absorption through the lining of the small intestine10. The polyphenols present in tea or red wine also inhibit iron absorption.1,5 Calcium and caffeine both inhibit the absorption of iron. It is recommended that people who are attempting to boost their iron levels should not consume caffeine within three hours before or after the consumption of a source of iron that is intended to be of benefit to them.8

Although an iron deficiency can result in a number of undesirable effects, it is the absorption of too much iron that can result in one's requiring emergent medical treatment. Thus, the focus of the rest of this paper will be on iron toxicity.

Once excess iron has been absorbed by the gut, the body has no means of eliminating it. Because elemental iron is so damaging to tissues, the body produces specific proteins that surround free iron and keep it away from living cells. Between 70 and 80 percent of free iron is sequestered inside the spherical molecule ferritin, and the remainder is bound within the protein homosiderin.11 Ferritin and homosiderin are formed in the liver, bone marrow, and spleen. When a cell needs iron, ferretin and homosiderin attach to a transport protein called transferrin and are delivered to the cells via the blood stream.5

Having too much iron in the body can result in a number of disorders, illness, and even death. For example, people who take iron supplements may be more prone to recurrent illnesses and infections due to malevolent bacteria in the body which thrive in iron-rich environments.4 Babies who are fed infant formula are often subjected to an unwarranted amount of supplemental iron in the formula. Normal human infants are born with enough iron in their tissues to support an entire year of growth, and therefore do not need iron supplements.4 Babies who are fed iron-fortified infant formulas can suffer from the proliferation of foreign bacteria in the gut, resulting in the production of gas, bloating, and the associated discomforts of these problems. Iron poisoning can occur if children consume adult doses of iron supplements, and toxicity has even been known to occur from cooking in cast iron pans.5,6 Other possible causes of excess iron in the body include repeated blood transfusions and chronic alcoholism.1

Four Phases of Iron Toxicity

Ingestion of iron in doses greater than 20 milligrams for each kilogram of body weight typically produce symptoms such as abdominal cramping, blackening of the stools, diarrhea, constipation, nausea, and vomiting. Ingestion of amounts greater than 60 milligrams per kilogram can cause internal hemorrhage, decreased blood pressure, and dehydration. A dose greater than 180 milligrams of iron per kilogram is often lethal.

Iron poisoning is divided into four phases. The first phase occurs in the first few hours after ingestion and involves acute gastric disturbances. The effects on the GI tract are due to the corrosiveness of the iron solution and include vomiting, diarrhea and abdominal pain. The disintegration of iron supplements results in a black coloration of the vomit and stools. If the corrosiveness of the iron is extensive, the mucosa of the upper GI tract may become hemorrhaged, wherein the vomit and stools will become red or reddish-brown with blood. If excessive blood and fluid is lost, the person who took the supplements may go into hypovolemic shock.

As free iron flows through the bloodstream the liver releases enzymes that cause blood vessels to dilate. Blood vessel dilation results in the lowering of blood pressure, which in turn can result in sleepiness or even coma. The blood also becomes acidic and the victim becomes at risk of having convulsions. Only a handful of iron poisoning victims die in the first phase if iron toxicity, and death in this stage is due to progressive circulatory failure and coma. However if the poisoning is mild, the patient usually recovers after the first phase without experiencing any additional phases.

The second phase of iron toxicity begins between 6 and 12 hours after the ingestion of excess iron. In the second phase the symptoms of the first phase abate as the iron is taken up by the liver. The lull in the symptoms lasts for 12 to 48 hours, and it is in this time that physicians may develop a false sense of security regarding a patient's recovery. Patients have been known to be sent home from a hospital Emergency Department during the second phase of iron toxicity because the physician mistakenly thought that the patient had recovered.9

The third phase of iron toxicity has a high mortality rate and is marked by severe shock, liver cell damage and cell death, decreased blood coagulation, low blood sugar, and renal failure.

If a patient survives the third phase of iron toxicity, in 2 to 5 weeks they will progress to the fourth phase of iron toxicity. In the fourth phase the patient develops symptoms of GI tract obstruction which include pain, constipation, and sometimes nausea and vomiting.

Treatment

In the prehospital setting, an emphasis should be placed on obtaining a thorough patient history and physical examination. Even though blood labs will inevitably be run at the hospital, an attempt should be made to ascertain the amount of elemental iron that the patient has ingested, as well as a good estimation of the patient's weight. The determination of amount of iron ingested will help to identify patients who are likely to advance to the third stage of iron toxicity. It is also useful to know if the supplements taken were time-release. Patients who have ingested toxic levels of iron should be monitored closely for patency of airway, adequacy of breathing, and effectiveness of circulation. Intravenous access should be obtained for maintenance of the patient's fluid requirements. Of particular importance in regards to IV access is the possibility of need for fluid resuscitation to replace those lost to hemorrhage and vomiting, as well as to maintain adequate blood pressure in the case of vasodilatation. A physician may choose to use drugs to increase blood pressure if needed.

Conclusion

Iron is a trace mineral that is required for the development of hemoglobin and myoglobin. The uptake of iron by the body is affected by other foods that are eaten; vitamin C helps the body absorb iron for example, whereas caffeine prevents the absorption of iron. Although iron is essential for life, too much of it can cause severe gastrointestinal problems and possibly even death. Children are more susceptible to iron poisoning because of their relatively smaller size/body weight. Management of iron poisoning in the prehospital setting hinges on finding out how much iron was taken, maintaining airway, breathing, and circulation, and transporting the victim to a hospital as soon as possible.

References

1. Daram, S. R., Havashi, P. H. (2005). Acute liver failure due to iron overdose in an adult. Southern Medical Journal, 98. 241-244
2. Hoekman, T. B. (date not given). Deferoxamine. In Heavy metal toxicology. Retrieved from https://www.luminet.net/~wenonah/hydro/heavmet.htm
3. Johnson, C. (2004). Iron overdose. Retrieved 4/17/2006, from https://www.nlm.nih.gov/medlineplus/ency/article/002659.htm
4. Healing with nutrition .com (2004). Iron. In Minerals (nutrient and health/disease associations). Retrieved from https://www.healingwithnutrition.com/mineral.html#iron
5. Johnson, C. (2004). Iron overdose. Retrieved 4/17/2006, from https://www.nlm.nih.gov/medlineplus/ency/article/002659.htm
6. Regional center for poison control and prevention serving Massachusetts and Rhode Island. Retrieved 5/2006 from https://www.maripoisoncenter.com/ctr/9704iron.html
7. Chapter 16: Acute metallic poisonings. In Matthew J, Lawson (Ed.), Treatment of common acute poisonings. 4th ed. Edinburgh: Churchill Livingstone; (1979): 129-138.
8. The Cleveland Clinic (2000). Are you meeting your iron needs? Retrieved 4/17/2006, from https://www.clevelandclinic.org/health/health-info/docs/1700/1753.asp?index=7240
9. Tox Pearls. In Collman, D., Plantz, S. H., Adler, J. (Eds.), Emergency medicine pearls of wisdom. 5th ed. Boston Medical Publishing; (2000): 176.
10. Phytochemicals. (date not given). Retrieved 5/9/06 from https://www.phytochemicals.info/phytochemicals/phytic-acid.php
11. Ferritin. (2006). Retrieved 5/9/06 from https://www.labtestsonline.org/understanding/analytes/ferritin/sample.html