Iron in tissue

Hereditary (primary) hemochromatosis is a very prevalent autosomal recessive disorder in certain parts of the world (eg, Scodand, Ireland, and North America). It is characterized by excessive storage of iron in tissues, leading to tissue damage. Total body iron ranges between 2.5 g and 3.5 g in normal adults in primary hemochromatosis it usually exceeds 15 g. The accumulated iron... 

The high-affinity uptake system is more puzzling. It requires a permease encoded by FTRI and an additional protein encoded by FET3.30/33 35 The Fet3 protein is a copper oxidoreductase related to ceruloplasmin (Section D). The protein Frelp (encoded by FRE1) is a metalloreductase that reduces Cu2+ to Cu+, as well as Fe3+ to Fe2+. It is essential for copper uptake (Section D).33 It has long been known that ceruloplasmin is required for mobilization of iron from mammalian tissues.30 Hereditary ceruloplasmin deficiency causes accumulation of iron in tissues.36 Yeast also contains both mitochondrial and vacuolar iron transporters.37/37a b... 

A severe decrease in P-globin levels leads to the precipitation of the a-chain, which in turn causes a defect in the maturation of the erythroid precursor, and erythropoiesis thus reducing red cell survival. The profound anemia in the affected individual stimulates the production of erythropoietin leading to the expansion of bone marrow and subsequent skeletal deformities. The hyperplasia of the bone marrow induces increased iron absorption leading to the deposition of iron in tissues. If the concentration of iron in the tissues becomes too high, it can lead to organ failure and death if appropriate therapeutic steps are not taken. 

WD-XRF wavelength dispersive-X-ray emission spectrometrywhich is visible microscopically siderosis deposition of iron in tissues and organs WHO World Health Organisation widy sign a dark pigment precipitation in hair roots at the fourth or fifth day after the intake of a toxic dose of thallium Wilson s disease recessive autosomal, hereditary disease (if untreated, results in invalidity and death) in which toxic amounts of copper are accumulated in the liver and central nervous system XPS X-ray photoelectron spectrometry XRF X-ray fluorescence spectrometry... 

The iron released may be measiu ed using a variety of methods based on two main techniques atomic absorption spectrometry (AAS) (flame or furnace) and ultraviolet (UV)-visible spectrophotometry. Flame AAS provides the reference method for determination of plasma iron. Protein precipitation with TCA is followed by centrifugation and measurement of iron in the supernatant by the absorption at 248.3 nm in an air-acetylene flame. While atomic absorption methods are routinely used for urine iron measurements, the need to remove protein and any hemoglobin contamination restricts the use of this technique in routine clinical chemistry for plasma iron. Electrothermal atomization AAS methods are typically used for determination of iron in tissues although inductively coupled plasma (ICP) is becoming more widely available. 

Ferritin is the major nonheme iron storage protein that is found in all tissues, but mostly in liver, bone marrow, and spleen [7]. Serum normally contains small quantities (<200-300 ng/mL) of ferritin, or isoferritins, that are derived from various tissues which can be quantitated by immunoassays. The concentration of serum ferritin correlates with the amount of nonheme iron in tissues... 

Transferrin is essential for movement of iron and without it, as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary atransferrinemia is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy (10). 

Copper is essential in animal metabolism. In some animals, such as the octopus and certain arthropods, it transports oxygen through the blood, a role performed by iron in mammals. As a result, the blood of these animals is green rather than red. In mammals, copper-bearing enzymes are necessary for healthy nerves and connective tissue. 

NADH, which enters the Krebs cycle. However, during cerebral ischaemia, metabolism becomes anaerobic, which results in a precipitous decrease in tissue pH to below 6.2 (Smith etal., 1986 Vonhanweh etal., 1986). Tissue acidosis can now promote iron-catalysed free-radical reactions via the decompartmentalization of protein-bound iron (Rehncrona etal., 1989). Superoxide anion radical also has the ability to increase the low molecular weight iron pool by releasing iron from ferritin reductively (Thomas etal., 1985). Low molecular weight iron species have been detected in the brain in response to cardiac arrest. The increase in iron coincided with an increase in malondialdehyde (MDA) and conjugated dienes during the recirculation period (Krause et al., 1985 Nayini et al., 1985). 

Gower, J.D., Healing, G. and Green, C.J. (1989b). Determination of desferioxamine-available iron in biological tissues by high-pressure liquid chromatography. Anal. Biochem. 180, 126-130. 

Figure 8.1 Body iron stores and daily iron exchange. The figure shows a schematic representation of the routes of iron movement in normal adult male subjects. The plasma iron pool is about 4 mg (transferrin-bound iron and non-transferrin-bound iron), although the daily turnover is over 30 mg. The iron in parenchymal tissues is largely haem (in muscle) and ferritin/haemosiderin (in hepatic parenchymal cells). Dotted arrows represent iron loss through loss of epithelial cells in the gut or through blood loss. Numbers are in mg/day. Transferrin-Tf haemosiderin - hs MPS - mononuclear phagocytic system, including macrophages in spleen and Kupffer cells in liver.

One of the most notable features of this inherited defect of iron homeostasis (Chapter 9) is the ability of individuals to accumulate large amounts of iron over many years and yet show no apparent adverse effects. This may in part be due to the ability of tissues, notably the liver, to increase their iron stores gradually over a long period of time, successfully sequestrating excess iron into ferritin and, predominantly, haemosiderin. However with time the excessive deposition of iron will cause a variety of toxic effects including diabetes and arthritis which are caused by deposition of iron in these tissues. Removal of this iron by venesection can often reduce these iron-induced symptoms. 

It has been reported that ceruloplasmin increases iron uptake into cultured human cells (Mukhopadhyay et al, 1998), although this apparently contradictory in vitro observation must be set against the in vivo evidence presented above from both animal and human studies. Plasma ceruloplasmin levels increase markedly in anaemia, consistent with a physiological role in tissue iron mobilization, and this effect is due to transcriptional activation of ceruloplasmin mRNA synthesis (Mukhopadhyay et al, 2000). 

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