Newborn pigs are iron deficient at birth and vulnerable to iron-deficiency anemia. Iron toxicosis in newborn pigs primarily occurs from administration of excess amounts of iron supplements by oral or parenteral routes. Vitamin E supplementation of the sow can help to prevent iron toxicosis in piglets.
Etiology of Iron Toxicosis in Newborn Pigs
Newborn piglets have low liver iron stores and receive only small amounts of iron in sow’s milk. Neonatal iron-deficiency anemia can occur in nonsupplemented piglets within 2–4 weeks after birth. Oral or parenteral iron supplementation is common practice but can result in peracute or acute toxicosis. Intravenous administration has the greatest potential for toxicity, followed by IM injection and oral administration.
Toxicokinetics of Iron Toxicosis in Newborn Pigs
Iron is absorbed in the small intestine by enterocytes in its ferrous (Fe2+) form and transferred to serum, where it is converted to its ferric (Fe3+) form and bound to transferrin. Dietary iron is poorly absorbed from the GI tract; uptake can be increased in the setting of iron deficiency.
Serum iron is primarily bound to transferrin, with lesser amounts bound to ferritin. Circulating serum iron constitutes a storage pool used for synthesis of hemoglobin, ferritin, cytochromes, and other iron-containing proteins. Of the total iron in the body, approximately two-thirds is bound to hemoglobin, 10% to myoglobin and iron-containing enzymes, and the remainder to the storage proteins ferritin and hemosiderin. Ferritin and hemosiderin are distributed throughout the body, with the highest concentrations found in the liver, spleen, and bone marrow.
Nonviable RBCs are removed from circulation by cells of the reticuloendothelial system in the liver, spleen, and bone marrow, where heme is broken down. Iron is heavily conserved and recycled.
Unless bleeding occurs, the body has a limited ability to excrete iron, such as through bile, feces (although most fecal iron comes from ingested iron that was not absorbed), urine, and GI tract mucosal sloughing.
Mechanism of Action
The mechanism of action of iron toxicosis is classified as via oxidative stress mediated by free radical formation. Free iron in excess of the body’s capacity to bind and sequester it generates free radicals that initiate biomolecular damage (cross-linking DNA, lipid peroxidation, and membrane damage). Ferrous iron (Fe2+) catalyzes formation of free radicals via the Fenton reaction. In fatal cases of toxicosis, it has been speculated that insufficient stores of antioxidants such as vitamin E can render affected piglets susceptible to the cytotoxic effects of increased reactive oxygen species (ROS) generated by iron at the cellular level. In the peracute, anaphylactoid form recognized in swine, damage to the tissues at and adjacent to the injection site is thought to cause release of potassium and other mediators of inflammation, resulting in cardiovascular collapse and sudden death, but the exact mechanism is not known.
Median Lethal Dose
The toxic dose of iron in humans is 200 and 250 mg/kg. The specific acute toxic dose of iron for swine is unknown but may be greater than that measured for humans.
Hooser SB. Chapter 36: Iron. In: Gupta RC. Veterinary Toxicology: Basic and Clinical Principles. 2nd ed. Elsevier, 2012.
Epidemiology of Iron Toxicosis in Newborn Pigs
Iron toxicosis in newborn pigs is relatively uncommon after injections of iron supplements, but it has been reported sporadically. These incidents are sometimes associated with vitamin E deficiency in the sows. Piglets born to sows deficient in selenium are also reportedly more susceptible to iron toxicosis. Morbidity and mortality can be high in affected litters.
Clinical Findings of Iron Toxicosis in Newborn Pigs
Iron toxicosis has been reported in a number of forms. In some litters, death occurs quickly, ranging from a peracute, anaphylactoid reaction, to acute iron toxicosis 2–6 hours after injection. In other, subacute cases, death can be delayed by 2–4 days.
The peracute, anaphylactoid form is characterized by sudden death minutes to a few hours after iron injection. In some ways, this resembles an anaphylactic reaction in its rapidity of onset, vascular collapse and death. In such cases, most of the litter can be affected.
In acute cases, in which death occurs 2–24 hours after onset, clinical signs can include pallor, vomiting, anorexia, respiratory distress, icterus, weakness, ataxia, inability to stand, muscle tremors, coma, and death. Swelling at the injection site is common.
In some cases of piglets that survive longer than 24 hours, death occurs as a consequence of liver damage, generalized weakness, and secondary infection.
In the 1970s, a rare but sometimes fatal syndrome of calcium mobilization with widespread calcification of tissues, referred to at the time as calciphylaxis, was recognized when vitamin D injections were administered at the same time as injections of iron. The syndrome was alleviated when vitamin D injections were administered at least 24 hours before iron injections.
Clinicopathologic findings of the acute form of iron intoxication include hyperkalemia and metabolic acidosis due lactic acidemia.
At necropsy, tissues around the injection site appear edematous, with yellowish-brown to black discoloration evident in regional lymph nodes. Icterus of tissues can be widespread, and multifocal petechial to ecchymotic hemorrhages are apparent. In some cases, frank hemorrhage secondary to liver rupture has been described. Periportal to diffuse, severe liver necrosis, as well as lesions of skeletal muscle, can be observed microscopically.
Diagnosis of Iron Toxicosis in Newborn Pigs
Diagnosis is generally made based on history, clinical signs, and selective, directed testing. Abdominal radiography may be useful to confirm ingestion by detecting intact iron tablets or iron concretions. Blood iron panels (measurement of serum iron concentration, total iron binding capacity [TIBC, an indirect measure of transferrin concentration], and percentage saturation of transferrin) are rarely used for diagnosis of iron excess. Electrolyte and acid-base status should be measured.
Treatment and Prevention of Iron Toxicosis in Newborn Pigs
There is no effective specific treatment for iron poisoning.
Intravenous fluid therapy should be administered as needed to maintain blood pressure. Acidosis with base deficits >10 mEq/L should be treated with isotonic sodium bicarbonate solution (1.3%), IV.
Deferoxamine, an iron-chelating drug, may be administered to animals with iron overload that survive the acute collapse (20–40 mg/kg daily in a continuous IV drip of sterile saline [0.9% NaCl] solution; infusion rate should not exceed 15 mg/kg/h). Approximately 140 mg of deferoxamine can bind 200 mg of iron or 1 g of ferrous sulfate.
The most important precipitating factor of iron toxicosis in pigs appears to be low vitamin E reserves in the sow. In such cases, either the piglets will be born deficient in vitamin E or the colostrum will not be able to provide adequate amounts of vitamin E to meet the antioxidant needs of the nursing animals, or both. Supplementing the sow’s diet with vitamin E, or administering injections of vitamin E during late gestation, will improve the status of the sow and help to prevent iron toxicosis in the piglets.
George L. Potbellied Pig Manual. UC Davis, 2012.
Iron toxicosis in newborn pigs primarily occurs from excess iron supplementation.
Peracute, acute, and subacute clinical forms of iron toxicosis are recognized in piglets.
Vitamin E supplementation of the sow can help to prevent iron toxicosis in piglets.