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Hepcidin is the master regulator of iron homeostasis.
Hepcidin functions to inhibit iron from entering circulation by binding ferroportin, the only transporter known to shuttle iron out of storage cells. This action effectively traps dietary iron in the duodenum, recycled iron from senescent red blood cells in macrophages, and the principal site of iron storage, hepatocytes.
The regulation of hepcidin expression is complex combining iron homeostasis, erythropoietic demand, and nutritional immunity. When plasma iron levels are high, hepcidin expression increases which stops more iron from entering circulation preventing a state of iron overload that could lead to the formation of reactive oxygen species. In the opposite scenario, when plasma iron is low, hepcidin expression is suppressed leading to an increase in iron entering circulation. In states of high erythropoietic demand brought on by blood loss or hypoxia, hepcidin is down-regulated allowing iron to flow to the bone marrow compartment for incorporation into new red blood cells. Iron is essential for all life, including pathogenic organisms. As such, a mechanism was developed to starve invading pathogens from utilizing the body’s iron in process called nutritional immunity. When the body senses the presence of a pathogen, hepcidin is highly upregulated locking away the body’s iron supply.
Structurally, hepcidin is a small, cationic peptide of the defensin family compacted by 4 disulfide bridges. It is principally expressed in the liver but localized production does occur in other tissues like the heart and brain
Physiologically, hepcidin can predict iron deficiency anemia as well as non-anemic iron deficiency. And, the route of iron supplementation can be predicted by indicating a patients responsiveness to oral iron.
When hepcidin levels decrease, plasma iron levels increase and, when hepcidin levels increase, plasma iron levels decrease.
Normal iron homeostasis is achieved when there is a balance of appropriate levels of plasma iron and hepcidin for physiological needs. However, when hepcidin regulation is disrupted, iron related diseases occur.
As the master regulator of iron homeostasis, hepcidin levels can predict iron deficiency in non-anemic patients before hemoglobin dips below the anemic threshold. While the prevalence of non-anemic iron deficiency is hard to estimate, there are approximately 23.4M Americans living with anemia, a number underrepresenting the iron deficient population in the US.
The upregulation of hepcidin during states of inflammation is responsible for anemia of inflammation. As such its levels can distinguish between iron deficiency anemia (low hepcidin) and anemia of inflammation (high hepcidin).
Unregulated iron can cause the formation of radical oxygen species (ROS) that lead to tissue damage. After trauma, seen post surgery or in critical care, hepcidin levels can predict the onset of acute kidney injury (AKI). Higher hepcidin locks away iron protecting the body from the creation of ROS therefore it may be important to ensure hepcidin levels are above a certain threshold before a surgery to minimize the risk of AKI post surgery.
Similar to the risk of AKI post surgery, hepcidin’s action to sequester iron from invading pathogens has predictive value for the 28-day mortality in septic patients.
Hepcidin’s role in controlling ferroportin expression effectively regulates iron absorption from the gut. As such, hepcidin can predict the responsiveness to oral iron which provides clinicians a decision point to prescribe oral iron, a cheap, non-invasive option, or require intra-venous iron administration.
Proper diagnosis is the key to improving care and avoiding morbidity in patients at risk from iron related conditions. Hepcidin, the master regulator of iron homeostasis, can shed light on a number of those conditions including iron deficiency, anemia of chronic disease, hereditary iron regulatory conditions, and a wide range of inflammatory or infectious agents. You can find hepcidin clinical testing services available at IntrinsicDx, the only CLIA certified, CAP accredited laboratory performing hepcidin testing in the US. Visit www.intrinsicdx.com for more information.
14 окт 2024
