Introduction Ironessentialmainly Iron is an essential element present mainly in heme of hemoglobin, myoglobin, cytochromes & in iron storage proteins ferritin & hemosidrin. An adult human has ~ 4 grams of iron in his body. Clinical importance: Clinical importance: - iron deficiency anemia - Iron deficiency in the body may lead to iron deficiency anemia (microcytic hypochromic anemia) haemosiderosis - Overdose of iron may cause haemosiderosis.
Dietary iron Recommended Dietary Allowance (RDA) Recommended Dietary Allowance (RDA) : Adults - Adults: 10 mg/day Females below 50 years & during lactation - Females below 50 years & during lactation: increased up to 15 mg/day Females during pregnancy - Females during pregnancy: increased up to 30 mg/day Sources of dietary iron: Sources of dietary iron: Animal sources - Animal sources: liver, spleen, meat (rich sources) Plant sources - Plant sources: molasses, dates, vegetables & whole cereals
Absorption of iron Site of absorption Site of absorption: mainly the duodenum On an average diet containing 10 – 15 mg of iron, only about 5 – 15% are absorbed. Factors affecting absorption of iron Factors affecting absorption of iron: Amount of iron ingested 1- Amount of iron ingested: increase in amount of iron in diet, increase amount absorbed State of iron 2- State of iron: Iron is liberated from organic complexes of diet (ferritin) by gastric HCl into organic salts. Fe2+ Then, Fe3+ liberated is reduced to Fe2+ by reducing substances in food as ascorbic acid (vitamin C). Iron of heme in meat is better absorbed (while still in heme molecule) Solubility of iron: 3- Solubility of iron: increase in pH causes decrease absorption of iron from GIT increase pH is caused by increased phosphates, oxalates, phytates & unabsorbed fatty acids in GIT.
Iron absorption Factors favouring absorption Factors reducing absorption Heme iron Ferrous form (Fe2+) Acids (HCl, vit. C) Solubilizing agents (sugars, aminoacids) Iron deficiency Increased erythropoiesis Pregnancy Hereditary hemochromatosis Inorganic iron Ferric form (Fe3+) Alkalis – antacids, pancreatic secretions Precipitating agents – phytates, phosphates Iron excess Decreased erythropoiesis Infections Tea Andrew NC. N Engl J Med 1999
Distribution of iron in the body Total iron in the body is ~ 4 grams Total iron in the body is ~ 4 grams This amount is available in two forms This amount is available in two forms: Functional forms (75%): 1- Functional forms (75%): Hemoglobin 1- Hemoglobin (67%) Myoglobin 2- Myoglobin (7.5%) Respiratory enzymes 3- Respiratory enzymes (0.5%): as cytochromes, etc
Distribution of iron in the body Non-functional forms (25%): 2- Non-functional forms (25%): Free iron is very toxic. So, iron is bound to proteins (non- heme metaloproteins) that allows it to be transported & stored in non-toxic forms. Transferrin 1- Transferrin (0.1%): for transport of iron in blood Ferritin hemosidrin 2- Ferritin & hemosidrin (24.9%): for storage of iron in tissues
Ferritin Ferritin: chief storage form of iron in tissues - is the chief storage form of iron in tissues. -is available in liver, spleen, bone marrow & intestinal mucosal epithelium. -is composed of a protein shell with a core containing iron as ferric form. 23% -Its Binding sites are saturated by 23% with iron. Iron storage in the body
Hemosiderin Hemosiderin : 35% - Similar to ferritin but with binding sites saturated by 35% iron. Increased in cases of excess iron in the body. - Increased in cases of excess iron in the body. Iron storage in the body
Hemoglobin of RBCs : 1- in Hemoglobin of RBCs : Hemoglobin contains 3.4 mg iron /gm of hemoglobin Hemoglobin is ~ 15 gm/100 ml blood Amount of iron in hemoglobin is ~ 50 mg/100 ml blood plasma 2- in plasma : Transferrin a) Transferrin : Iron is carried in blood by transferrin, which carries two atoms of F3+ per molecule. Only about 30% of transferrin is saturated with iron (called Total Iron Binding capacity, TIBC) Only about 30% of transferrin is saturated with iron (called Total Iron Binding capacity, TIBC) Transferrin is synthesized in the liver & runs with the -globulin in electrophoresis. Blood iron
iron deficiency anemia In iron deficiency anemia, plasma iron is reduced while TIBC tends to. liver disease In liver disease, both plasma iron & TIBC are decreased tends to increase. liver disease In liver disease, both plasma iron & TIBC are decreased Plasma ferritin b ) Plasma ferritin : Plasma contains very low concentrations of ferritin (20 – 250 g/L) Plasma ferritin is a good index of iron storage It is decreased in iron deficiency anemia & is increased in hemosiderosis. Blood iron
Excretion of iron feces 1- in feces (90 – 95%): unabsorbed iron Fecal iron is mainly unabsorbed iron. urinesweat 2- in urine & sweat (5 - 10%) Daily loss of iron in urine & sweat is about 0.5 – 1 mg of iron. menstruationmilk 3- in menstruation & milk (5 - 10%) About 15 – 30 mg of iron (in the form of hemoglobin) is lost in menstruation per month (0.5 – 1 mg/day). Lactation leads to loss of 0.5 – 1 mg of iron per day
Iron Scavenging Intravascular haemolysis :Breakdown of red cells in the circulation – Free haemoglobin binds haptoglobins -> taken up by liver – Free haem binds haemopexin -> taken up by liver – Haem passing through kidney reabsorbed
Laboratory assessment of iron status 1- Plasma iron 2- Plasma ferritin 3- Plasma transferrin, Total Iron Binding Capacity (TIBC) & TIBC Saturation
Plasma iron 1- Plasma iron : limited diagnostic value -Measurement of plasma iron is of limited diagnostic value as: Level fluctuate widely in healthy 1- Level fluctuate widely in healthy due to many factors (as diurnal rhythm, menstruation, oral contraceptive pills intake, pregnancy, etc) not provide an adequate index of iron status 2- Measurement of plasma iron do not provide an adequate index of iron status as: In cases of iron deficiency anemia, plasma iron is reduced late when iron is entirely depleted from iron stores. In iron overdose, plasma iron is elevated late when iron stores are seriously overloaded with iron. Plasma iron alters in cases not associated with changes in iron stores 3- Plasma iron alters in cases not associated with changes in iron stores as in acute infections or trauma, in which plasma iron is rapidly reduced to low levels while iron stores are not affected Laboratory assessment of iron status (cont.)
Plasma ferritin 2- Plasma ferritin: body iron stores Plasma ferritin is closely related to body iron stores whether low, normal or high. (while plasma iron becomes abnormal only in presence of gross abnormalities) Low (or upper normal) plasma ferritin Low (or upper normal) plasma ferritin indicates depleted iron stores. High plasma ferritin High plasma ferritin indicates iron overdose (hemosiderosis). acute phase reactants N.B. Plasma ferritin is one of the acute phase reactants. So, it is elevated in acute disorders as infections….etc Laboratory assessment of iron status (cont.)
Plasma transferrin & Total Iron Binding Capacity (TIBC) 3- Plasma transferrin & Total Iron Binding Capacity (TIBC): - reduced - Transferrin level is reduced in protein malnutrition, chronic liver diseases, acute infections & neoplasm. (low protein synthesis by the liver) increasedin iron deficiency (as a compensatory mechanism) - Transferrin synthesis is increased in iron deficiency (as a compensatory mechanism) Transferrin can be measured: Directly - Directly Indirectly - Indirectly by Total Iron Binding capacity (TIBC): TIBC is the ability of transferrin to bind iron. 30-40% of binding sites of transferrin are occupied by iron. Laboratory assessment of iron status (cont.)
Iron deficiency Commonest single nutrient deficiency worldwide. Causes of iron deficiency Causes of iron deficiency: Deficient intake of iron 1- Deficient intake of iron: ingestion diet poor in iron for a long time Increased requirements of iron 2- Increased requirements of iron : as in pregnancy, lactation & menstruation Impaired absorption of iron 3- Impaired absorption of iron: due to intestinal causes (malabsorption syndrome) Excessive loss of iron 4- Excessive loss of iron: in cases of chronic bleeding (from GIT bleeding etc..) Laboratory & clinical manifestations: ferritin 1- low plasma ferritin transferrin (& TIBC) 2- Then, increase transferrin (& TIBC) plasma iron 3- Then, low plasma iron anemialab 4- Finally, anemia is evident by lab investigation (microcytic hypochromic anemia) & by clinical clinical manifestations
Iron overload (iron toxicity) The body is unable to excrete large load of iron (bound to proteins) Amount of iron in the body is controlled by regulating its absorption from GIT rather than its excretion. Some people can absorb large amounts of iron, from intestine (20- 45% of intake), leading to accumulation of excessive amounts of iron in tissues, a hemosiderosis condition known as hemosiderosis (hemosiderin accumulates in tissues). Haemochromatosis Haemochromatosis means hemosiderosis with injury to involved tissues.
Causes of iron overload Causes of iron overload: 1- Increased intake & absorption Acute overdose: causes fatal symptoms due to the toxic effects of free iron in plasma. Chronic overload: with increased absorption of iron due to any cause for long duration. Parentral administration of iron 2- Parentral administration of iron including repeated blood transfusion. Genetic haemochromatosis 3- Genetic haemochromatosis. Laboratory Investigations: Plasma iron 1- Plasma iron is elevated (especially in late cases) Transferrin 2- Transferrin becomes 70-90% saturated with iron (TIBC saturation) Plasma ferritin 3- Plasma ferritin is elevated. Iron overload (iron toxicity) Iron overload (iron toxicity) cont.
Iron Toxicity Iron can damage tissues Iron can damage tissues Catalyzes the conversion of hydrogen peroxide to free-radical ions Catalyzes the conversion of hydrogen peroxide to free-radical ions Free-radicals can attack: Free-radicals can attack: – cellular membranes – Proteins – DNA Iron excess possibly related to cancers, cardiac toxicity and other factors Iron excess possibly related to cancers, cardiac toxicity and other factors