Iron deficiency anemia in inflammatory bowel disease

Figure 1 Causes of iron deficiency anemia. GI: Gastrointestinal; NSAIDs: Nonsteroidal anti-inflammatory drugs.

Figure 2 Role of hepcidin in the regulation of iron homeostasis. Fe³⁺ is reduced to Fe²⁺ by enterocyte brush border reductase Dcytb, transported across brush border membrane by DMT1. If iron demand is low, Fe²⁺ is stored as ferritin and sloughed with enterocytes. If iron demand is high, iron is oxidized by oxidase hephaestin and then exported into the plasma at the basolateral membrane by ferroportin[23]. Hepcidin binds to iron exporter, ferroportin 1, leading to its phosphorylation, internalization by binding to JAK 2 and lysosomal degradation, thus preventing iron release into the plasma[16]. DcytB: Duodenal ferric reductase; DMTI: Divalent metal transporter 1.

Figure 3 Signaling pathways regulating hepcidin expression in the liver. Enterocyte iron induces BMP6 expression. BMP6 is released via the portal vein to act on cell-surface receptors in the liver, BMPR-I, BMPR-II, and HJV, a co-receptor of BMP, leading to phosphorylation of cytosolic transcription factors, SMAD 1/5/8, which complex with SMAD 4[16,21]. This heteromeric complex translocates to the nucleus and enhances transcription of hepcidin gene, HAMP. In iron deficiency, HJV is cleaved by matriptase-2 activation reducing BMP signaling, and BMP is sequestered by s-HJV, preventing its interaction with plasma membrane HJV, decreasing hepcidin expression[21]. IL-6: Interleukin 6; BMP: Bone morphogenetic protein; HJV: Hemojuvelin; s-HJV: Soluble HJV; TfR2: Transferrin receptor 2; HFE: Hereditary hemochromatosis protein; BMPR: Bone morphogenetic protein receptors.

Figure 4 Management of iron deficiency anemia in patients with inflammatory bowel disease[16]. Hb: Hemoglobin; IDA: Iron deficiency anemia; TSAT: Transferrin saturation; CRP: C-reactive protein; IBD: Inflammatory bowel disease; IV: Intravenous; ESA: Erythropoiesis stimulating agents.