Plasma iron

Determinations of plasma Iron, total Iron-binding capacity (TIBC), and % transferrin saturation... 

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.

Fluxes of iron from the plasma towards BM and other tissues can be quantified by ferrokinetic studies, using 59Fe and sophisticated computer models (Ricketts et ah, 1975 Ricketts and Cavill, 1978 Barosi et ah, 1978 Stefanelli et ah, 1980). Plasma iron turnover (PIT), erythroid iron turnover (EIT), non-erythroid iron turnover (NEIT), marrow iron turnover (MIT), and tissue iron turnover (TIT) could be calculated in many disorders of iron metabolism and in all kinds of anaemias. Iron is rapidly cleared from the plasma in iron deficiency and in haemolytic anaemias. If more iron is needed for erythropoiesis, more transferrin receptors (TfR) are expressed on erythroblasts, resulting in an increased flux of iron from intestinal mucosal cells towards the plasma. In haemolytic anaemias MPS, and subsequently hepatocytes, are overloaded. In hereditary haemochromatosis too much iron is absorbed by an intrinsic defect of gut mucosal cells. As this iron is not needed for erythropoiesis,... 

The peculiar thing in hereditary haemochromatosis (HH) is that the intestinal mucosal cell behaves essentially like an iron deficient cell. Iron absorption is always high if related to the body s iron needs. In HH subjects with normal plasma ferritin values, both mucosal uptake and mucosal transfer of iron often exceed values found in patients with uncomplicated iron deficiency (Marx, 1979b). In fact the situation with respect to iron absorption in mature intestinal mucosal cells, as depicted in Figure 9.4(b), is identical to that in iron deficiency, except for the difference in plasma iron saturation. It was already known that mucosal cells in HH contain no ferritin, explaining the high mucosal transfer of iron (Francanzani... 

This receptor-mediated endocytotic pathway has been especially well studied in the uptake of iron from blood plasma. Iron, because of its very low-solubility product (< 1(T17 at pH 7.4), is transported in plasma bound to the iron-binding protein transferrin. Two Fe3+ ions bind to each transferrin molecule. Entry into... 

These are generated by the liver during infections and other forms of inflammatory challenge, as part of the acute-phase response. This response to infection is characterised by fever, sleep, adrenotrophic hormone release, decreased plasma iron and zinc levels, elevated neutrophils in the bloodstream and enhanced cytokine production. These changes, part of the body s response to combat infection, occur within hours. The elevated temperatures may inhibit the replication of some bacteria and viruses and may also enhance the function of some immune cells. 

Adverse reactions include the following Hives rashes angioedema nausea, dyspepsia (5% to 25%) heartburn epigastric discomfort anorexia massive Gl bleeding occult blood loss potentiation of peptic ulcer persistent iron deficiency anemia prolongation of bleeding time leukopenia thrombocytopenia purpura decreased plasma iron concentration shortened erythrocyte survival time fever thirst dimness of vision. 

The iron is transferred by the mucosal epithelium to the body and is bound to plasma transferrin in the ferric state. In the plasma, iron takes part in a dynamic transferrin-iron equilibrium and is distributed into vascular and interstitial extravascular compartment. 50 to 60% of transferrin is extravascular. The plasma iron pool in adults is about 3 mg and has an estimated turnover of 20 to 30 mg per 24 hours. Daily and obligatory losses of iron in healthy men are about 1 mg in healthy menstruating women these average 2 mg and in either case are compensated by a net absorption of 1 to 2 mg from the intestine, which enters the mobile pool of transferrin iron. 

Heinemann G. [Plasma iron, serum copper, and serum zinc during therapy with ovulation inhibitors.JMed Klin 1974 69(20) 892-6. 

Schade reviewed (114) the earlier studies on the role of serum transferrin in iron transport. Various early investigators had observed that the blood serum transferrin rapidly bound iron administered either through the gastrointestinal tract or by intravenous injection. There was a rapid turnover of iron in the blood serum and the degree of saturation of the transferrin was related to the amount of iron administered. In no instances, however, was the blood serum transferrin ever saturated with iron. Jandl et al. (71) have shown that both ovotransferrin and serum transferrin can transport plasma iron into red cells and that the transport is dependent on the concentration of transferrin. Iron taken up by the blood cells could not be eluted by subsequent incubation with iron-free transferrin solutions. More recently Morgan and Laurel (99) reported that iron uptake in reticulocytes is independent of the transferrin concentration. The iron complex of serum transferrin has a higher affinity for immature red cells than does the iron-free protein (72). Both bind specifically to immature red cells and the attachment permits the cells to remove the iron. Once the iron is removed, however, the iron-free transferrin can be replaced by an iron-transferrin complex. 

Mazur, A., S. Green, and A. Charleton Mechanism of plasma iron incorporation into hepatic ferritin. J. Biol. Chem. 235, 595 (1960). 

Schade, A. L. Plasma iron Its Transport and significance. Nutrition Rev. 13,... 

Under normal circumstances, transferrin is one-fourth to one-third saturated with iron. The level of saturation may decrease in systemic infection or cancer and in iron deficiency anemia, the most common nutritional deficiency in the United States. In individuals with iron deficiency anemia, transferrin levels are increased. The level of saturation with iron increases in iron overload syndromes such as hereditary hemochromatosis or as a result of repeated blood transfusions, as is the case in thalassemia patients. Determinations of total plasma iron (TI) and plasma total iron binding capacity (TIBC) are routinely performed in the clinical biochemistry laboratory. The TIBC value reflects transferrin levels in plasma the amount of iron that can be bound by transferrin is equal to TIBC x 0.7. Total plasma iron levels in iron deficiency anemia become abnormal before hemoglobin levels show any change. 

Low iron levels in human blood were observed by clinicians to be associated with infectious diseases. A decrease in plasma iron levels was induced by bacterial infections (33, 34) or by treatment with bacterial endotoxins (35). The treatment of animals with endotoxin-released mediator of hypoferremia protected them from lethal salmonellosis (36). Although the levels of hypoferremia or degrees of iron saturation of Tr were not examined in these studies, various experiments indicated that the fall in serum iron increased resistance to bacterial infections. 

The determination of plasma iron and iron binding capacity... 

There are conflicting results on the possible relation between plasma iron concentrations and movement disorders (SEDA-19, 45). A significant correlation between serum ferritin concentrations and the severity of chor-eoathetoid movements has been observed (303). All 30 subjects had a minimum lifetime cumulative exposure to typical neuroleptic drugs of 3 years. Nevertheless, and as was stated by the authors, it is unclear whether higher body iron stores exacerbate the symptoms of tardive dyskinesia or predispose to its development. 

If the Interaction of Iron and zinc were functionally proximal to the site of the regulation of Iron by the state of Iron reserves of the host, then differences In Iron nutrlture would not affect the uptake of zinc In the presence of Iron (Fig 6). We found an Inverse correlation with a correlation coefficient of -0.546 (p <0.05) between the Increment In circulating zinc after ingesting a 2 1 ferrous Iron zinc solution and plasma Iron concentration. Thus, It would appear that the Interaction of iron and zinc occurs after the Intestinal regulation of Iron. 

Oral iron therapy should not be given 24 h before i.m. injections begin and for 5 days after the last i.v. injection not only is continuation unnecessary, but it may promote adverse reactions by saturating the plasma protein (transferrin) binding capacity so that the injected iron gives a higher unbound plasma iron concentration than is safe. 

Subsequently, desferrioxamine should be administered by i.v. infusion not exceeding 15 mg/kg/h (maximum 80 mg/kg/24 h) or further i.m. injections (2 g in sterile water 10 ml) should be given 12-hourly. Poisoning is severe if the plasma iron concentration exceeds the total iron binding capacity (upper limit 75 mmol/1) or the plasma becomes pink due to the large formation of ferrioxamine (see below). If severe poisoning is suspected i.v. rather than i.m. administration of desferrioxamine is indicated without waiting for the result of the plasma concentration. 

Cottin, Y. Doise, J. M. Maupoil, V. Tanniere-Zeller, M. Dalloz, F. Maynadie, M. Walker, M.K. Louis, P. Carli, P.M. Wolf, J.E. Rochette, L. Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction. Fundam. Clin. Pharmacol. 12 236-241. 1998. 

The early, dose-related type of chloramphenicol toxicity is usually seen after the second week of treatment, and is characterized by inhibited proliferation of erythroid cells and reduced incorporation of iron into heme. The clinical correlates in the peripheral blood are anemia, reticulo-cytopenia, normoblastosis, and a shift to early erythrocyte forms. The plasma iron concentration is increased. Early erythroid forms and granulocyte precursors show cytoplasmic vacuolation. After withdrawal, complete recovery is the rule. Leukopenia and thrombocytopenia are less frequent. 

Iron toxicity can be expected if the amount of free iron released into the plasma exceeds the plasma iron-binding capacity. This is more likely to occur when using iron sorbitol-citric acid complex (iron sorbitex), since the iron is less firmly bound than with iron dextran. Several conditions associated with low iron-binding capacity, such as malnutrition (kwashiorkor, malnutrition syndrome) and previous or simultaneous oral iron therapy appear to predispose to the development of these toxic reactions. In addition, folic acid deficiency has been reported to be a predisposing factor (SED-9, 516), the likely mechanism being altered iron utilization secondary to folic acid deficiency, which results in an increased saturation of ironbinding capacity. 

However, toxic reactions to intravenous iron occur when ionized iron exceeds plasma binding capacity. With iron dextran, the iron moiety is so firmly bound to dextran that ionized iron does not exceed plasma ironbinding capacity even when total plasma iron concentrations are extremely high. However, there are adverse effects, which were at first underestimated whenever possible other routes or methods of iron dextran administration should be preferred. 

In animal and in vitro studies, inhaled nitric oxide has led to surfactant inactivation and promotion of oxidative and nitrosylative lung injury (2). These effects have not been reported during clinical use of inhaled nitric oxide at concentrations less than 80 ppm. In a review of two articles it was noted that nitric oxide does not increase the risk of chronic lung disease of the newborn, despite speculation that it may increase chronic lung disease of prematurity due to the formation of nitrogen dioxide and peroxynitrite, in addition to membrane lipid peroxidation and increased unbound plasma iron in preterm infants (7). 

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