Acute iron toxicity is seen almost exclusively in young children who accidentally ingest iron tablets. As few as 10 tablets of any of the commonly available oral iron preparations can be lethal in young children. Adult patients taking oral iron preparations should be instructed to store tablets in child-proof containers out of the reach of children. Children who are poisoned with oral iron experience necrotizing gastroenteritis with vomiting, abdominal pain, and bloody diarrhea followed by shock, lethargy, and dyspnea. Subsequently, improvement is often noted, but this may be followed by severe metabolic acidosis, coma, and death. Urgent treatment is necessary. Whole bowel irrigation (see Chapter 58) should be performed to flush out unabsorbed pills. Deferoxamine, a potent iron-chelating compound, can be given intravenously to bind iron that has already been absorbed and to promote its excretion in urine and feces. Activated charcoal, a highly effective adsorbent for most toxins, does not bind iron and thus is ineffective. Appropriate supportive therapy for gastrointestinal bleeding, metabolic acidosis, and shock must also be provided.
B. Chronic Iron Toxicity
Chronic iron toxicity (iron overload), also known as hemochromatosis, results when excess iron is deposited in the heart, liver, pancreas, and other organs. It can lead to organ failure and death. It most commonly occurs in patients with inherited hemochromatosis, a disorder characterized by excessive iron absorption, and in patients who receive many red cell transfusions over a long period of time (eg, individuals with β-thalassemia).
Chronic iron overload in the absence of anemia is most efficiently treated by intermittent phlebotomy. One unit of blood can be removed every week or so until all of the excess iron is removed. Iron chelation therapy using parenteral deferoxamine or the oral iron chelators deferasirox or deferiprone (see Chapter 57) is less efficient as well as more complicated, expensive, and hazardous, but it may be the only option for iron overload that cannot be managed by phlebotomy, as is the case for many individuals with inherited and acquired causes of refractory anemia such as thalassemia major, sickle cell anemia, aplastic anemia, etc. Deferiprone rarely has been associated with agranulocytosis; thus weekly monitoring of the CBC is required for patients treated with this drug.
Vitamin B12 (cobalamin) serves as a cofactor for several essential biochemical reactions in humans. Deficiency of vitamin B12 leads to megaloblastic anemia (Table 33–2), gastrointestinal symptoms, and neurologic abnormalities. Although deficiency of vitamin B12 due to an inadequate supply in the diet is unusual, deficiency of B12 in adults—especially older adults—due to inadequate absorption of dietary vitamin B12 is a relatively common and easily treated disorder.
Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin B12 is from microbial synthesis; the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin B12 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin B12 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12.