Suspected iron overload or high serum ferritin

Chapter 37 SUSPECTED IRON OVERLOAD OR HIGH SERUM FERRITIN






IRON METABOLISM


Iron is present at about 35–45 mg/kg body weight in men and women respectively (typically 2–3 g). Iron uptake in the gut is the key step regulating iron stores and is stimulated by iron deficiency and chronic anaemia. Approximately 10%–20% of dietary iron (1–2 mg/day) is absorbed in the proximal small intestine. Once in enterocytes, iron needs to be released into the circulation, where it complexes with transferrin to be transported around the body. Iron is used in a variety of essential proteins including haemoglobin (60%–70% of body stores); and myoglobin, cytochromes and other cellular enzymes (10% of body stores). The liver is the principal storage site for iron (typically 20%–30% of body stores), in protein, ferritin; and in haemosiderin, where it can be detected histologically with Perl’s stain. Iron is lost from the body (about 1 mg/day) in bile and urine, and with the shedding of enterocytes and skin. In women, iron is also lost with menses and pregnancy. In pathological states, iron can be depleted by gastrointestinal blood loss and excessive menstrual losses.





Causes of high serum ferritin


Serum ferritin is increased in iron overload, liver injury and in inflammatory states. Iron overload can occur with inherited abnormalities of iron metabolism, particularly hereditary haemochromatosis (HFE), repeated blood transfusion and dietary iron overload (including hazardous alcohol consumption). The most common cause of iron overload in Western countries is haemochromatosis. There are a number of different types of haemochromatosis. HFE1 is the most common type of haemochromatosis and is an autosomal recessive condition caused by mutation of the HFE gene, in particular a cysteine to tyrosine mutation at amino acid 282, designated Cys282Tyr or C282Y. This mutation interferes with the regulated movement of iron from enterocytes into the body, so that iron accumulation can occur despite adequate iron stores. This depends on factors like dietary iron intake, and iron depletion through blood loss or pregnancy. The C282Y mutation appears confined to populations with Northern European ancestry and in these groups the prevalence of C282Y homozygotes is about 1 in 200 to 1 in 400. Approximately 50% of C282Y homozygotes will develop significant iron overload, depending on diet, blood loss and other genetic factors. Another HFE mutation that appears to play a role in HFE1 is the H63D mutation, which seems to only be associated with iron overload in combination with C282Y. Other genes implicated in haemochromatosis include transferrin receptor 2, ferritin heavy chain, ferroportin 1, hepcidin and hemojuvelin.

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Mar 29, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Suspected iron overload or high serum ferritin

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