Iron physiology

normal iron physiology

1. NORMAL IRON PHYSIOLOGY NIKHIL GUPTA MBBS - 2011

2. SOURCES OF IRON Heme iron :- Liver Meat Poultry Fish Non Heme iron :- Leafy vegetables Legumes Beans Cereals Milk

3. DAILY REQUIREMENT Children (ages 1-10): 7 to 10 mg per day. Women (ages 19-50): 18 mg per day. Pregnant Women: 27 mg per day. Lactating Women: 9 to 10 mg per day. Men (ages 19 and older): 8 mg per day

4. DISTRIBUTION Total body iron = 3 to 5 grams 60 to 70 % - Hemoglobin. 15 to 30 % - stored in liver and RE system as ferritin and hemosiderin . 4 % - Myoglobin . 0.1 % - B lood plasma as transferrin .

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6. ROLE OF IRON IN THE BODY Hematopoiesis . Found in Hemoglobin and myoglobin . Cytochrome P450 superfamily and catalase, which metabolize drugs and degrade hydrogen peroxide. C onversion of blood sugar to energy. Production of enzymes ,new cells, amino acids, hormones and neurotransmitters. Proper immune system functioning. Physical and mental growth.   

7. ABSORPTION 1-2 mg absorbed daily. From duodenum and upper jejunum. Heme iron is better absorbed than non heme iron. Ferric Iron(III) is reduced to ferrous iron(II ) by D cyt -b (duodenal cytochrome b ). Taken up through the DMT1 (divalent metal transporter 1) protein. Heme iron is taken up through the Heme Transporter.

8. Once in the enterocytes, iron is exported through the membrane protein ferroportin 1 into the plasma. Some of it can be stored as ferritin ,depending on the current iron requirement of the body. Iron(II) in the plasma is immediately oxidised to iron(III) by hephaestin or ceruloplasmin . The iron(III) binds to transferrin and is transported with the blood stream to the target cells for utilization.

9. Control of iron absorption M ucosal block theory

10. FACTORS AFFECTING ABSORPTION Enhancers :- Vitamin C Cooking in iron vessels Gastric acid Cysteine Sugar Amino acid Lactate Pyruvate Inhibitors :- Tannins Phosphates Oxalates Pancreatic secretions Antacids Calcium Tetracyclines

11. UTILIZATION Attachment of iron-transferrin complex to specific Transferrin receptors TfRs on RBCs and other cells. Complex engulfed by endocytosis . Iron dissociates from complex at acidic pH of endosomes. Released iron is utilized . Tf and TfR are returned to cell surface to carry fresh loads.

12. STORAGE In tissues-as ferritin & hemosiderin . In blood-as transferrin . Excess iron in the blood is deposited especially in liver hepatocytes & in the reticulo -endothelial cells of the bone marrow. This may lead to iron toxicity.

13. EXCRETION Daily excretion in adult male = 0.5-1 mg mainly as exfoliated GI mucosal cells , RBCs and in bile. Very little in urine and sweat. In women, additional menstrual loss of blood may bring iron loss average upto 1.5 mg per day.

14. FP Ferroportin Hc Mediated by hepcidin - produced by the liver in response to increased iron availability or stores. Hepcidin downregulates ferroportin in enterocytes-blocks iron absorption from the intestine. REGULATION OF IRON LEVELS

15. DEFICIENCY OF IRON CAUSES- chronic bleeding. excessive menstrual bleeding. GIT bleeding (ulcers, hemorrhoids, Ulcerative Colitis etc.). inadequate intake. substances (in diet or drugs) interfering with iron absorption. malabsorption  syndromes. Inflammation. 

16. SYMPTOMS anemia fatigue dizziness pallor hair loss irritability weakness brittle or grooved nails glossitis GLOSSITIS BRITTLE GROOVED NAILS

17. WHEN DOES IRON BECOME A PROBLEM? Normally 3 – 5 g of iron in the body. Tissue damage when total body iron is 7 – 15 g. 3 commonly encountered forms of chronic overload: 1- Primary haemochromatosis 2- Transfusion-associated haemochromatosis 3- Dietary causes

18. EFFECTS OF IRON OVERLOAD Cardiac failure Liver cirrhosis/fibrosis/cancer Diabetes mellitus Infertility Growth failure

19. 1. Primary Haemochromatosis (chronic iron toxicity) Excessive absorption of iron from the gut Iron accumulates in the liver, heart and pancreas & damages these organs by free radical production gives the skin a bronze color Therapy : Phlebotomy (removal of 0.5 l of blood): a decrease of iron in the circulation leads to iron mobilisation from stores

20. 2. Secondary haemochromatosis Due to multiple frequent blood transfusions in thalassemia major, sickle cell anaemia Therapy : iron chelators 3. Dietery causes ( Acute iron poisoning ) among people who are exclusively cooking in iron pots due to ingestion of iron tablets (15-20) - fatal poisoning in young children. Vomiting, diarrhoea , cyanosis, hemetemesis , convulsions, acidosis, shock, death Therapy : iron chelator-desferoxamine