Iron poisoning is often listed in the classic metabolic acidosis mnemonic MUDPILES, but how does it cause an anion gap metabolic acidosis?

HOW? The mechanism appears to be multi-factorial.

  1. Acute excessive ingestion of iron causes direct corrosive damage to the GI tract.
  2. Free iron penetrates numerous organs such as the liver. It enters hepatocytes, damaging the mitochondria (disrupts oxidative phosphorylation) and increases lipid peroxidation. It also damages microsomes, and other cellular organelles.
  3. Excessive iron can affect the heart: resulting in fatty necrosis of the myocardium, increased capillary permeability, and a reduction in cardiac output.
  4. Free iron also stimulates the release of pro-dilatory agents such as serotonin and histamine resulting in hypo perfusion, anaerobic metabolism and lactic acidosis.
  5. In addition ferrous iron is converted to ferric iron; hydrogen ions are released, adding to the metabolic acidosis.

The profound damage to the liver results in: hypoglycemia, hyperammonemia, coagulation defects,

and hepatic encephalopathy occurs in the context of fulminant liver failure.
REFERENCES
  1. Goyer RA. Toxic effects of metals. Klaassen CD, ed. Casarett & Doull’s toxicology:the basic science of poisons. 5th ed. New YorkCity, NY: McGraw-Hill, 1996;715-716.
  2. Williams RJ. Biomineralization: iron and the origins of life. Nature 1990;343:213-214.4.
  3. Osweiler GD, Carson TL, Buck WB, et al. Iron. Clinical and diagnostic veterinary toxicology. 3rd ed. Dubuque, Iowa: Kendall/Hunt Publishing Co, 1985;104-106.5.
  4. Hillman RS. Hematopoietic agents: growth factors, minerals, and vitamins. Hardman JG, Limbird LE, Molinoff PB, et al, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York City, NY: McGraw-Hill,1995;1311-1340
  5. Proudfoot AT, Simpson D, Dyson EH. Management of acute iron poisoning. Med Toxicol. 1986 Mar-Apr;1(2):83-100.
  6. Greentree WF, Hall JO. Iron toxicosis. Bonagura JD, ed. Kirk’s current therapy XII small animal practice. Philadelphia, Pa: WB Saunders Co, 1995;240-242.3.

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