RBC Metabolism & Disorders of Iron (PDF)

‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ RBC METABOLISM & DISORDER OF THE IRON Objective...

‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ RBC METABOLISM & DISORDER OF THE IRON Objectives:- To understand:- -Understanding the general structural & functional features of red blood cells (RBCs). - Recognizing the main metabolic pathways occurring in RBCs with reference to their relations to functions of RBCs. -Role of G6PD in protecting cell from oxidative damage -Essential iron compounds -Iron metabolism -Biochemical function of iron -Laboratory assessment of iron status -disorder of iron metabolism 1  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Introduction to the Red Blood Cells (RBCs) The red blood cells (RBCs) are not true cells. RBCs contain no nucleus or nucleic acids, and thus, cannot reproduce. RBCs contain no cell organelles (as mitochondria, Golgi, ER or lysosomes) and thus possess no synthetic activities (no protein biosynthesis, no lipid synthesis & no carbohydrate synthesis). RBCs must be able to squeeze through some tight spots in microcirculation. For that RBCs must be easily & reversibly deformable Biochemical composition of the RBCs Red cells contain 35 % solids. Hemoglobin, the chief protein of the red cells. Other proteins are present in combination with lipids and oligosaccharide chains, forming the stroma and cell membrane. Potassium, magnesium, and zinc concentrations in red cells are much higher than in the plasma. 2  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Functions of RBCs RBCs have relatively simple functions as they have much simpler structure than most human cells. The major functions of RBCs are delivering oxygen to the tissues & disposal of carbon dioxide & protons formed by tissue metabolism. This function is carried out by hemoglobin. Metabolism of RBCs RBCs contain no mitochondria, so there is no respiratory chain, no citric acid cycle, and no oxidation of fatty acids or ketone bodies. Energy in the form of ATP is obtained only from the glycolytic breakdown of glucose with the production of lactate (anaerobic glycolysis). ATP produced being used for keeping the biconcave shape of RBCs & in the regulation of transport of ions & water in and out of RBCs. Metabolic pathways of RBCs metabolism; 3  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ 1-Glucose transport through RBC membrane: Glucose is transported through RBC membrane glucose by a facilitated diffusion by glucose transporters (GLUT-1). Glucose transporters (GLUT-1) are independent on insulin i.e. insulin does not promote glucose transport to RBCS 2- Glycolysis: Glucose is metabolized in RBCs through anaerobic glycolysis (that requires no mitochondria and no oxygen). One molecule of glucose yields 2 molecules of ATP by one anaerobic glycolytic pathway. In addition, 2 molecules of lactate are produced. Lactate is transported to blood & in the liver it is converted to glucose. 3- Production of 2,3 bisphosphoglycerate (2, 3 BPG): In RBCs, some of glycolysis pathways are modified so that 2, 3 bisphosphoglycerate is formed (by bisphosphoglyceratemutase). 2, 3 bisphosphoglycerate decreases affinity of Hb for oxygen. So, it helps oxyhemoglobin to unload oxygen. Storing blood results in decrease of 2,3-BPG leading to high oxygen affinity Hb. This leads to oxygen trap. 6-24 hours are needed to restore the depleted 2,3 BPG Maximum storage time for RBCs is 21-42 days 4  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ 4-Pentose phosphate pathway: RBCs contain an active pentose phosphate pathway (PPP) for glucose that supplies NADPH (PPP is the only source for NADPH in RBCs) NADPH is important in keeping glutathione in the reduced glutathione. Reduced glutathione plays a very important role in the survival of the red blood cells. (prevents oxidation of membrane) Role of G6PD in protecting the cells from oxidative damage Glucose 6-phosphate dehydrogenase is the first enzyme of pentose phosphate pathway & its deficiency leads to reduced production of NADPH ending in acute hemolytic anemia. Essential iron compounds -Iron is an essential element present mainly in the porphyrin complex, haem, and in iron storage proteins, ferritin and haemosiderin. Haem, which is present in haemoglobin, myoglobin and cytochromes, is formed by the insertion of ferrous iron, Fe2+, into protoporphyrin which itself is synthesised by a complex chain of reactions. 5  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ -The adult human possesses about 70 mmol (4 g) of iron. Iron balance is regulated by alterations in the intestinal absorption of iron. -The normal intake of iron is about 0.2–0.4 mmol/day (10–20 mg/day). Good sources are liver, fish and meat. RDA (recommended dietary allowances) 6  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ -Adult man & postmenopausal women: 10 mg -Premenopausal women: 15to 20 mg -Pregnant women: 30 to 60 mg Women require greater amount than men due to physiological loss during menstruation. Biochemical functions -Iron is a component of several functionally important molecules. -Iron is required for the synthesis of hemoglobin, myoglobin, cytochromes, catalase and peroxidase. -Cytochromes & certain non-heme proteins are necessary for ETC & oxidative phosporylation. -Peroxidase, the lysosomal enzyme is required for phogocytosis & killing of bacteria. -Iron is also essential for the synthesis of non heme iron (NHI) compounds like, succinate dehydrogenase, iron-sulfur proteins of flavoproteins, NADH dehydrogenase. -Iron helps mainly in the transport, storage and utilization of oxygen. -Iron is associated with effective immuno- competence of body 7  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Iron metabolism iron absorption -about 5–10% of dietary iron is absorbed by an active transport process. Most absorption occurs in the duodenum. -Iron is called as one way substance, because it is absorbed and excreted from small intestine.Iron is absorbed from upper small intestine. -Iron is absorbed in three forms: (1) ferrous iron 2))ferric iron (3) heme iron.Iron is absorbed mainly in the ferrous form. Ferric ions are reduced with ascorbic acid & glutathione of food to more soluble ferrous (Fe2+) form which is more readily absorbed than Fe3+ -The rate of absorption is controlled by physiological and dietary factors: State of iron stores in the body: Absorption is increased in iron deficiency and decreased when there is iron overload. Rate of erythropoiesis: When this rate is increased, absorption may be increased even though the iron stores are adequate or overloaded. Contents of diet: Substances that form soluble complexes with iron (e.g. ascorbic acid) facilitate absorption. Substances that form insoluble 8  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ complexes (e.g. phytate) inhibit absorption. The chemical state of the iron: Iron in the diet does not usually become available for absorption unless released during digestion. This depends, at least partly, on gastric acid production; Fe2+ is more readily absorbed than Fe3+, and the presence of H+ helps to keep iron in the Fe2+ form. Iron in haem (in meat products) can be absorbed while still contained in the haem molecule. Iron transport, storage and utilization -After being taken up by the intestinal mucosa, iron is either (1) incorporated into ferritin and retained by the mucosal cells, or (2) transported across the mucosal cells directly to the plasma, where it is carried mainly combined with transferrin -Iron retained by mucosal cells is lost from the body when the cells are sloughed. Mucosal cell retention is influenced by the body’s iron status, being reduced in iron depletion and increased in states of iron overload. -The total iron circulating bound to transferrin is normally about 50–70 μmol (3–4 mg). -Iron in plasma is taken up by cells and either incorporated into haem or stored as ferritin (or 9  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ haemosiderin, probably formed by the condensation of several molecules of ferritin). -Iron released by the breakdown of Hb, at the end of the erythrocyte’s life, is normally effi ciently conserved and later reused. Storage -Iron is stored in liver, spleen & bone marrow in the form of ferritin. -In the mucosal cells, ferritin is the temporary storage form of iron. -Ferritin contains about 23% iron. -Ferritin in plasma level is elevated in iron over load. -Ferritin level in blood is an index of body iron stores. -Ferritin is an acute phase reactant protein, elevated in inflammatory diseases. -Hemosiderin:It is another iron storage protein, which can hold about 35% of iron by weight. -Hemosiderin accumulates when iron levels are increased 10  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Summary of the absorption, transport and utilisation of iron. Total body iron stores (g) for the main iron containing proteins as shown on the right side of the figure. Iron excretion and sources of loss 11  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Iron excreted in the faeces is principally exogenous, that is, dietary iron that has not been absorbed by the mucosal cells and transported into the circulation. In males, there is an average loss of endogenous iron of about 20 μmol/day (1 mg/day) in cells desquamated from the skin and the intestinal mucosa. Females may have additional losses due to menstruation or pregnancy. Urine contains negligible amounts of iron. Laboratory assessment of iron status This is necessary in the investigation of iron deficiency states and iron overload. The following tests are used: - 1-serum iron This is of limited diagnostic value, since levels fluctuate widely in health. Much of this variation appears to be random, but some specific causes can be recognized:  Diurnal variation, with higher values in the morning.  Menstrual cycle, with low values just before and during the menstrual period.  Oral contraceptives, which cause increased serum [iron]  Pregnancy, which tends to cause increased serum [iron]. However, it is often accompanied by iron deficiency so that serum [iron] falls. Measurements of serum [iron] do not provide an adequate index of iron status. Although plasma [iron] is low in iron deficiency and is raised in iron overload, these changes occur relatively late when iron stores have already become either completely depleted or seriously overloaded. In addition, serum [iron] also alters in conditions not associated with changes in iron stores. Acute infections or trauma 12  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ precipitate a rapid fall in serum [iron]. Chronic inflammatory disorders (e.g. rheumatoid arthritis) and malignant diseases are also associated with low levels. Serum [iron] determination is only required for diagnostic purposes for a few conditions, for example in suspected cases of acute iron poisoning and in the assessment of individuals with an increased risk of hemochromatosis. 2-Serum ferritin Serum [ferritin] is closely related to body iron stores, whether these are decreased, normal or increased, whereas serum [iron] becomes abnormal only in the presence of gross abnormalities of iron storage. A low, or low normal serum [ferritin] indicates the presence of depleted iron stores. However, since ferritin is an acute-phase reactant, levels may be increased in patients with iron deficiency and concurrent inflammation, malignancy or hepatic disease, although at concentrations greater than 100 μg/L iron deficiency is almost certainly not present. Increased serum [ferritin] is found in iron overload, irrespective of the cause, and in many patients with liver disease or cancer. A normal serum [ferritin] virtually excludes untreated iron overload. Determination of serum [ferritin] currently provides the most useful measure of iron status widely available on a routine basis. 3-Serum transferrin, total iron-binding capacity and iron saturation Normally, nearly all the iron-binding capacity in serum is due to transferrin, and about 40% of the binding sites on transferrin are occupied by iron. Transferrin has a much longer half-life than iron, and serum [transferrin] shows fewer short-term fluctuations. [Transferrin] can be measured not only directly, but also indirectly as the ability of serum protein (largely transferrin) to bind iron, the so- called TIBC of serum. The ratio of serum [iron] to [transferrin] (or TIBC) then determines the transferrin (or TIBC) saturation. In iron- deficiency anaemia, the low serum [iron] is typically associated with an increase in transferrin concentration (and TIBC). This leads to a 13  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ low saturation of transferrin (and TIBC) with iron. Conversely, in iron overload, serum [iron] is high and transferrin is normal or low, that is, a high percentage saturation of TIBC. Important of measurement ;  in the detection of early or latent haemochromatosis  in patients being treated with erythropoietin for the anaemia of chronic renal failure, the percentage saturation of TIBC provides a better index of available iron than serum [ferritin],  the serum transferrin (or TIBC) is also helpful in determining the significance of very high serum [ferritin] in patients with disordered liver function of unknown cause, in whom the differential diagnosis may be between haemochromatosis and malignancy. A high serum [ferritin] in the absence of an increased percentage saturation of TIBC indicates that cancer is more likely to be the diagnosis. 4-Serum transferrin receptor A circulating form of the transferrin receptor, lacking the cytoplasmic and transmebrane domains of the intact receptor, has been identified in serum. Its concentration rises in iron deficiency following the depletion of iron stores and, because levels are unaffected by inflammation, its measurement has the potential to provide an indication of iron status in patients with anemia associated with chronic disease. Disorders of iron metabolism -Iron deficiency & iron overload are the major disorders of iron metabolism. Iron deficiency -Iron deficiency causes a reduction in the rate of haemoglobin synthesis & erythropoiesis. 14  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ -It can result in iron deficiency anemia. -Causes: **Iron deficiency is caused by inadequate intake, impaired absorption, chronic blood loss & increased demand. **Iron deficiency anemia mostly occurs in growing children, adolescent girls, pregnant & lactating women. In patients who develop iron deficiency, serum [ferritin] falls, then serum [transferrin] and TIBC increase, after which serum [iron] falls, and finally anaemia becomes evident. -Clinical features **Microcytic hypochromic anemia in which the size of the red blood cells are smaller than normal and have much reduced haemoglobin content. **Weakness, fatigue, dizziness and palpitation ** Nonspecific symptoms are nausea, anorexia, constipation, and menstrual irregularities. Iron over load This is much less common than iron deficiency. Diagnosis is not usually difficult once the possibility has been considered. Increased serum [iron] with normal [transferrin] (or TIBC) often lead to 100% saturation of transferrin (or TIBC). Serum [ferritin] is increased, often to more than 1000 μg/L. More common causes are as follows: Increased intake and absorption. Acute overdose, mainly occurring in children, may cause severe or even fatal symptoms, due to the toxic effects of free iron in plasma. Chronic overload occurs when the diet contains excess absorbable iron (e.g. acid-containing food cooked in iron pots). Iron deposits form, for example, in the liver 15  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ causing hepatic fibrosis and in the myocardium causing myocardial damage. Parenteral administration of iron, including repeated blood transfusions. Hereditory haemochromatosis  Haemosiderosis and haemochromatosis and iron poisoning are conditions associated with iron over load. Haemosiderosis: It refers to accumulation of hemosiderin (intracellular) in liver & other reticulo-endothelial system. There is no significant tissue destruction. Haemosiderosis is an initial stage of iron over load. Haemochromatosis Haemochromatosis is a clinical condition in which iron is directly deposited in the tissues (liver, spleen, pancreas & skin). Hereditary haemochromatosis This autosomal recessive disorder is associated with a mutation of the HFE gene, which is located on chromosome 6. In 85–90% of cases, the mutation is due to a single base change that results in the substitution of tyrosine for cysteine at position 282 of the HFE protein (C282Y). Individuals homozygous for this mutation are predisposed to an unregulated increase in the intestinal absorption of dietary iron although the phenotypic expression is variable. At least 90% of symptomatic individuals are male, suggesting that iron losses in menstruation and pregnancy may protect females. 16  ‫ زﻳﻨﺐ ﺳﻌﺪ‬.‫د‬ ‫ﺟﺎﻣﻌﻪ وارث اﻻﻧﺒﻴﺎء‬ Lec 1,2&3 ‫ﻛﻠ ﻴ ﻪ ا ﻟ ﻄ ﺐ‬ ‫ﻓ ﺮ ع ا ﻟ ﻜ ﻴ ﻤ ﻴ ﺎ ء ا ﻟ ﺤ ﻴﺎ ﺗ ﻴ ﻪ و ا ﻟ ﺴ ﺮ ﻳ ﺮ ﻳﻪ‬ Iron poisoning This is potentially life threatening, particularly in children. Early clinical symptoms, which include epigastric pain, nausea and vomiting, often with haematemesis, may settle but be followed later by acute encephalopathy and circulatory failure. Acute liver and renal failure may also develop. Treatment involves giving desferrioxamine, an iron- chelating agent, which binds the iron in plasma, and the resulting complex is excreted in urine. Serum iron values greater than 90 μmol/L require treatment. An immediate IM injection of desferrioxamine is followed by gastric lavage, leaving desferrioxamine in the stomach. 17