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IRON M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
Iron (Fe) • 2 types of body iron • heme iron • hemoglobin, myoglobin, catalases, peroxidases, cytochromes (a, b and c – involved in electron transport), cytochrome P450 (involved in drug metabolism) • non-heme iron • ferritin, hemosiderin, hemofuscin, transferrin, ferroflavoproteins, aromatic amino acid hydroxylases • food iron is also classified as heme and non-heme
Food iron heme iron • meats • poultry • fish 20-23% of heme-iron is absorbable non-heme iron • vegetables • fruits • legumes • nuts • breads and cereals only ~ 3% on non heme iron is absorbed
Iron absorption • occurs in upper part of small intestine • about 10% of food iron is absorbed • requires gastric HCl (releases ionic iron) • also requires copper • ferrous is better absorbed than ferric form • Fe++ forms chelates with ascobic acid, certain sugars and amino acid
Iron distribution and storage • carried in blood stream via transferrin (a b globulin) • stored in 2 forms: • ferritin (a water soluble complex consisting of a core of ferric hydroxide and a protein shell (apoferritin) • hemosiderin (a particulate substance consisting of aggregates of ferric core crystals) • stored in liver, spleen, bone marrow, intestinal mucosal cells and plasma
Iron elimination • there is no mechanism for excretion of iron • iron is normally lost by exfoliation of intestinal mucosal cells into the stools • trace amounts are lost in bile, urine and sweat (no more than 1 mg per day) • bleeding (vaginal, intestinal) is a more serious mechanism of elimination
IRON DEFICIENCY Initial symptoms are vague and ill-defined • easy fatigability • lack of appetite • headache • dizziness • palpitations then: hypochromic-microcytic anemia • microcytosis (small RBCs) • hypochromia (poor fill of hemoglobin) • poikilocytosis (bizarre shapes) • anisocytosis (variable sizes)
IRON DEFICIENCY Causes: • excessive blood loss (parasitic, accidental, menstrual): is most common cause • rapid growth in children with limited intake of iron • malabsorption • gastric resection • sprue • increased metabolic requirement • pregnancy, lactation or neoplasia
Diagnosis of iron deficiency • hematology (microcytic hypochromic cells) • low serum iron • low serum ferritin( indicates low body stores) • in some conditions (inflammation, hepatitis) ferritin may be high • low hemosiderin • high total iron binding capacity (TIBC)
Iron absorption • average diet contains 10 - 15 mg of iron perday • a normal person absorbs 5 -10% of this iron or 0.5 - 1.0 mg daily • iron absorption increases in response to low iron stores • menstruating women: 1 - 2 mg per day • pregnant women: 3 - 4 mg per day • absorption is via active process
Different types of iron • Ferrous sulfate 20% • Exsiccated ferrous sulfate • ferrous gluconate 11.6% • ferrous fumarate 33% • ferrocholinate 12% • polysaccharide-iron complex • iron dextran (Imferon)
Treatment of iron deficiency • give 200 - 400 mg of iron per day • up to 25% of the iron preparation may be absorbed • 50 - 100 mg of iron may be utilized in case of deficiency • give on an empty stomach • enteric coated iron tablet should not be used since we want absorption to occur in the stomach and proximal duodenum
Treatment of iron deficiency • parenteral iron is used in patients who have had bowel resections or in cases of inflammatory bowel disease • normally given IM (painful) Z-track minimizes tatoo • oral iron causes black stools, constipation, cramping • do not administer with antacids or metal chelators (tetracyclines)
Acute iron toxicity common in small children ingesting large doses of soluble iron compounds toxicity is usually divided into 4 phases: 1. 30 - 60 min. following ingestion • abdominal pain • nausea and vomiting • signs of acidosis and cardiovascular collapse may be seen
Acute iron toxicity 2. Period of improvement - last about 8 to 16 hours 3. Period of progressive cardiovascular collapse (about 24 hrs after ingestion) • convulsions • coma • high mortality 4. Gastrointestinal obstruction from scarring of stomach and small intestine
Deferoxamine mesylate (DFOM) A chelating agent which reacts with ferric ion to form a 1:1 chelate known as ferrioxamine Marketed as Desferal Injection (Ciba) Produced by Streptomyces pilosus
Chronic iron toxicity • causes • hereditary hemochromatosis • hemosiderosis • symptoms • cirrhosis: iron deposition in the liver • diabetes: iron deposit in the pancreas (damage to beta cells) • skin pigmentation • cardiac failure • treatment: phlebotomy ( 1 unit of blood removes about 250 mg of iron