Transferrin iron deficiency

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). 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

Transferrin binds iron, transporting it to sites where it is required. Ferritin provides an intracellular store of iron. Iron deficiency anemia is a very prevalent disorder. Hereditary hemochromatosis has been shown to be due to mutations in HFE, a gene encoding the protein HFE, which appeats to play an important role in absorption of iron. 

RLS is a neurologic medical condition characterized by an irresistible desire to move the limbs. It is thought that these abnormal sensations are a result of iron deficiency in the brain and iron-handling abnormalities in the CNS. Iron and H-ferritin concentrations, along with transferrin receptor and iron transporter numbers, are reduced in the substantia nigra of patients with RLS.20 These iron abnormalities lead to dysfunction of dopaminergic transmission in the substantia nigra. 

Total iron-binding capacity (TIBQ—quantifies the ironbinding capacity of transferrin and is increased in iron-deficiency anemia... 

Transferrin saturation (serum iron/TIBC)—indicates the amount of transferrin that is bound with iron it is lower in iron-deficiency anemia. 

Females 30-160 mcg/dL (5.4-31.3 pmol/L) transferrin low in iron-deficiency anemia. 

Transferrin saturation (TSAT) Other Tests 30-50% (0.30-0.50) Transferrin saturation = (serum iron/TIBC) x 100 a saturation of less than 15% is common in iron-deficiency anemia. 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

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 earliest and most sensitive laboratory change for iron-deficiency anemia is decreased serum ferritin (storage iron), which should be interpreted in conjunction with decreased transferrin saturation and increased total iron-binding capacity (TIBC). Hb, hematocrit, and RBC indices usually remain normal until later stages of iron-deficiency anemia. 

Transferrin 8-9 Binds iron in plasma and transports iron to bone Iron deficiency, pregnancy, hypoxia, chronic blood loss, estrogens Chronic infection, cirrhosis, burns, enteropathies, nephrotic syndrome, cortisone, testosterone... 

Iron(III) citrate, " " or iron(III) ammonium citrate, is the usual vehicle for administering supplementary iron to an iron-deficient patient, for inducing iron-overload in rats or other creatures prior to testing the efficacy of iron chelators, or for introducing the isotope Fe for metabolic tracer studies. Stability constants for the aqueous iron(III)-citrate system have been established. " The 2 1 complex is claimed to be the dominant species in iron(III)/citrate/DMF systems. " There has been a very qualitative study of the incorporation of iron into transferrin from iron citrate. " Iron(III) citrate reacts relatively slowly with the aluminum(III)-transferrin complex to give the thermodynamically strongly favored combination of iron(III)-transferrin with aluminum(lll) citrate. " The mechanism of iron uptake from citrate complexes in cells has been briefly discussed. An octa-iron citrate complex appears in Section 5.4.5.4.3 below. 

Functional iron deficiency may develop with normal ferritin levels but low transferrin saturation (less than 20%), presumably due to the inability to mobilize iron stores rapidly enough to support increased erythropoiesis. Underlying infectious, inflammatory, or malignant processes. 

Mechanism of Action An enzymatic mineral that is an essential component in the formation of Hgb, myoglobin, and enzymes. Promotes effective erythropoiesis and transport and utilization of oxygen (Oj). Therapeutic Effect Prevents iron deficiency. Pharmacokinetics Absorbed in the duodenum and upper jejunum. Ten percent absorbed in patients with normal iron stores increased to 20%-30%in those with inadequate iron stores. Primarily bound to serum transferrin. Excreted in urine, sweat, and sloughing of intestinal mucosa. Half-life 6 hr. 

Increased erythropoiesis is associated with an increase in the number of transferrin receptors on developing erythroid cells. Iron store depletion and iron deficiency anemia are associated with an increased concentration of serum transferrin. 

A system of internal iron exchange exists which is dominated by the iron required for hemoglobin synthesis. For formation of red blood cells, iron stores ean furnish It)—U> ingAl of iron, as compared to 1-1 mg from dietary sources Only ca 10 wl r+ of ingested iron actually is absorbed. Transferrin is essential for movement of iron and without it. as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary. iiransferrinemui is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy. 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

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. 

Normal range for TI is 50-160 fig/dL in males TIBC is 250-400 /ng/dL, and transferrin is 200-400 mg/dL (mean is 295). Even though TI is a low normal and transferrin is a high normal, saturation is only 12%, and we can conclude that the patient is mildly iron-deficient. 

Transferrin levels increase in iron deficiency anemia. Ferritin levels decrease. Transferrin binds Fe3+ to its amino acid side-chains, while ferritin binds Fe3+ as ferric hydroxide micelles. 

Perhaps the most dramatic indication of the indispensable role of transferrin as an iron donor, however, is provided by an experiment of nature. Individuals afflicted with atransferrinemia, a genetic inability to synthesize transferrin, suffer from a paradoxical co-existence of iron deficiency anemia and generalized iron overload (68, 69). Without transferrin, neither the delivery of iron to hemoglobin-synthesizing cells nor its mobilization from stores is successfully regulated. 

The diagnosis of iron deficiency has its difficulties and ambiguities. Severe iron deficiency can be detected easily by the marked reduction in hemoglobin concentration, mean corpuscular hemoglobin and decreased serum iron concentration. However, in mild iron deficiency hemoglobin concentration, transferrin saturation, and serum ferritin levels are frequently normal in patients with depleted bone... 

Riboflavin deficiency is associated with hypochromic anemia as a result of secondary iron deficiency. The absorption of iron is impaired in riboflavin-deficient animals, with a greater proportion of a test dose retained in the intestinal mucosal cells bound to ferritin, and hence lost in the feces, rather than being absorbed. The mobilization of iron bound to ferritin, in either intestinal mucosal cells or the liver, for transfer to transferrin, requires oxidation of Fe + to Fe +, areaction catalyzed by NAD-riboflavinphosphateoxidoreductase (Powers et al., 1991 Powers, 1995 Williams et al., 1995). 

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