Iron overloadIron overload or haemochromatosis (also spelled hemochromatosis in American English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosis (HH or HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions. Organs most commonly affected by hemochromatosis include the liver, heart, and endocrine glands.
TransferrinTransferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein. Transferrin glycoproteins bind iron tightly, but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of total body iron, it forms the most vital iron pool with the highest rate of turnover (25 mg/24 h).
Interleukin 6Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1 and its activation of IL-1ra and IL-10.
HepcidinHepcidin is a protein that in humans is encoded by the HAMP gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. During conditions in which the hepcidin level is abnormally high, such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red blood cells.
Iron-deficiency anemiaIron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, short of breath, or having decreased ability to exercise. Anemia that comes on quickly often has more severe symptoms, including confusion, feeling like one is going to pass out or increased thirst. Anemia is typically significant before a person becomes noticeably pale.
CirrhosisCirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years.
FerroportinFerroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene, and is part of the Ferroportin (Fpn) Family (TC# 2.A.100). Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. Ferroportin is the only known iron exporter. After dietary iron is absorbed into the cells of the small intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream.
COVID-19Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the virus SARS-CoV-2. The first known case was identified in Wuhan, China, in December 2019. The disease quickly spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‐19 are variable but often include fever, cough, headache, fatigue, breathing difficulties, loss of smell, and loss of taste. Symptoms may begin one to fourteen days after exposure to the virus. At least a third of people who are infected do not develop noticeable symptoms.
Acute-phase proteinAcute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response). The acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating neutrophils and their precursors.
Chronic kidney diseaseChronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include (in chronological order) high blood pressure (often related to activation of the renin–angiotensin system system), bone disease, and anemia.
Reactive oxygen speciesIn chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () produces superoxide (), which is the precursor to most other reactive oxygen species: O2{} + e^- -> \ ^\bullet O2- Dismutation of superoxide produces hydrogen peroxide (): 2 H+{} + 2 \ ^\bullet O2^-{} -> H2O2{} + O2 Hydrogen peroxide in turn may be partially reduced, thus forming hydroxide ions and hydroxyl radicals (), or fully reduced to water: H2O2{} + e^- -> HO^-{} + \ ^\bullet OH 2 H+ + 2 e- + H2O2 -> 2 H2O In a biological context, ROS are byproducts of the normal metabolism of oxygen.
Iron deficiencyIron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key component of the hemoglobin protein, acting as a transport medium for electrons within the cells in the form of cytochromes, and facilitating oxygen enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death.
AnemiaAnemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. The name is derived from ἀναιμία anaimia, meaning 'lack of blood', from ἀν- an-, 'not' and αἷμα haima, 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise.
C-reactive proteinC-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.
