Iron overload syndromes and the liver

Pathology Lab, Division of Gastrointestinal Pathology, Minnesota Gastroenterology, Abbott Northwestern Hospital, Minneapolis, MN, USA.
Modern Pathology (Impact Factor: 6.19). 03/2007; 20 Suppl 1(1):S31-9. DOI: 10.1038/modpathol.3800715
Source: PubMed


Iron can accumulate in the liver in a variety of conditions, including congenital, systemic iron-loading conditions (hereditary hemochromatosis), conditions associated with systemic macrophage iron accumulation (transfusions, hemolytic conditions, anemia of chronic disease, etc), in some hepatitidies (hepatitis C, alcoholic liver disease, porphyria cutanea tarda), and liver-specific iron accumulation of uncertain pathogenesis in cirrhosis. The anatomic pathologist will be faced with the task of determining whether iron accumulation in the liver is significant and, if so, the nature of the disease that lead to the accumulation (ie diagnosis). The tools available to the pathologist include (most importantly) histologic examination with iron stain, quantitative iron analysis, clinical history, laboratory iron tests (serum iron and iron-binding capacity, serum ferritin) and germline genetic analysis for mutations in genes known to be associated with hemochromatosis (HFE, ferroportin, hepcidin, hemojuvelin, transferrin receptor-2). This article provides an overview of the above.

1 Follower
8 Reads
  • Source
    • "Although our data showed a tendency for hepatic and renal iron accumulation in ms/− males compared with +/− animals (Figure 6A and 6C), the differences in non-haem iron content between these mice were not significant (P values >0.05). In general, the ferritin level serves as a marker of iron loading in cells and tissues [45]. Moreover, it is usually elevated in the kidneys and liver under conditions of haemolysis [29], [46]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism.
    PLoS ONE 09/2014; 9(9):e107641. DOI:10.1371/journal.pone.0107641 · 3.23 Impact Factor
  • Source
    • "Importantly, humans do not have an iron excretion pathway and therefore excess iron is usually stored primarily in the liver, spleen, and bone marrow in the form of ferritin molecules [1]. However, under certain pathological conditions, an excess accumulation of free iron in the body occurs as a consequence of enhanced dietary uptake (hemochromatosis), medical treatment (chronic blood transfusions ), destabilized hemoglobin (sickle cell disease), reduced hemoglobin (thalassemia), or as a result of conditions such as cardiomyopathies, hepatic fibrosis and diabetes mellitus [2] [3] [4] [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Desferrioxamine (DFO) is used to treat an excess accumulation of iron in the body and is currently the most commonly used iron chelator for the treatment of 'iron overload' disorder. However, the disadvantages of DFO surround its high toxicity and very short plasma half-life. Here, the detailed in vitro evaluation of a novel class of high molecular weight iron chelators based on DFO and polyethylene glycol methacrylate is reported. Reversible addition fragment chain transfer (RAFT) copolymerization afforded polymer conjugates (P-DFO) with well-controlled molecular weight (27-127 kDa) and substitution of DFO (5-26 units per chain) along the copolymer. Human umbilical vein endothelial cell (HUVEC) based cell viability assays showed that the cytotoxicity of P-DFO decreased more than 100-fold at identical concentrations of DFO. The hemocompatibilities of various P-DFO samples were determined by measuring prothrombin time (PT), activated partial thromboplastin time (APTT), thrombelastograph parameters (TEG), complement activation, platelet activation, and red blood cell aggregation. Furthermore, the iron binding properties and chelating efficiency of P-DFO were compared to DFO by measuring the spectral properties upon binding to iron(III), while the prevention of iron(III) mediated oxidation of hemoglobin was also determined. Degradation of the P-DFO conjugates via cleavable ester linkages between the polymer backbone and the PEG side chains was evaluated using gel permeation chromatography (GPC) and NMR. Since the chelating ability of DFO remains intact after conjugation to the copolymer backbone, these macromolecular, blood compatible and degradable conjugates are promising candidates as long circulating, non-toxic iron chelators.
    Biomaterials 11/2008; 30(4):638-48. DOI:10.1016/j.biomaterials.2008.09.057 · 8.56 Impact Factor

Show more

Similar Publications

Preview (2 Sources)

8 Reads
Available from