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Hemoglobin synthesis includes globin and heme synthesis.The heme molecule is formed by combining Fe2+ ions with protoporphyrin in bone marrow cells.
Iron obtained from iron preparations is excreted from the body in a similar manner to dietary iron.Iron is primarily stored and circulated in the body with minimal loss.Very limited losses are estimated at approximately 1 mg/day mainly due to sweating and epithelial shedding of the skin, genitourinary tract, and gastrointestinal tract. For women, menstrual bleeding is another route of iron loss.
Iron toxicity and treatment
As a strong catalyst, iron is responsible for converting the reduced form of O2 into harmful hydroxyl radicals in the body.Excess iron can lead to high doses of reactive oxygen species (ROS).High doses of ROS are cytotoxic and cause chronic and acute inflammation.It is therefore essential to regulate iron levels with iron-binding proteins,such as transferrin for iron transport and import into cells, and ferritin for iron storage.These iron regulatory proteins prevent the accumulation of toxic cytosolic iron, thereby maintaining a balance between cellular iron uptake and storage.During iron overload, protective mechanisms are insufficient to limit cytosolic iron concentrations.A large iron load cannot match the storage capacity of ferritin.High concentrations of iron enter the bloodstream as toxic non-transferrin-bound plasma iron (NTBI).In the worst case, high cellular iron concentrations accelerate the uptake of non-transferrin iron, leading to the accumulation of NTBI.
NTBI is cytotoxic due to its ability to promote the formation of free hydroxyl radicals (a type of ROS), an injury that leads to mitochondrial swelling and lysis.Siderophore cells deplete mitochondrial ATP content and eventually die.In addition to the toxic mechanism, iron poisoning is divided into four clinical phases The first phase is the initial stage of excess iron in the intestinal system and circulation.High iron concentrations cause hemorrhagic necrosis and ulceration of the upper intestinal tract, leading to disruption of the intestinal mucosal barrier and blood loss. In addition, the development of NTBI can lead to circulatory collapse and decreased consciousness.The second stage is more stable, with increased awareness. Decreased plasma iron levels due to cellular uptake create a false sense of security.
The third stage is the most dangerous stage due to intracellular iron toxicity.Iron catalyzes the inner mitochondrial membrane, leading to peroxidative damage and disordered oxidative phosphorylation.ATP synthesis is blocked, leading to cellular dysfunction and even death.Hypotension, which recurs 2 to 5 days after iron ingestion, is associated with severe organ dysfunction, primarily involving the liver, heart, and brain. Sudden onset of severe hepatic failure with possible hypoglycemia, coagulopathy, and exacerbated metabolic acidosis with fatal outcome.
Stage IV is rare because a small number of cases of iron poisoning can survive stage III.Patients who survive to stage 3 may develop narrowing or obstruction of the bowel due to scarring.Treatment of iron overload includes gastrointestinal (GI) decontamination, chelation, and supportive care.Whole bowel irrigation can be performed with a large osmotically balanced polyethylene glycol electrolyte solution to flush excess iron from the GI tract. In severe cases, an iron chelator, such as deferoxamine, may be given intravenously. It binds iron and other metal ions with chelating agents and is excreted in urine.Patients with dyspnea and gastrointestinal distress may also require supportive care, providing mechanical ventilation and fluid replacement, respectively.