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NORMAL 
IRON PHYSIOLOGY 
NIKHIL GUPTA 
MBBS - 2011
SOURCES OF IRON 
Heme iron :- 
• Liver 
• Meat 
• Poultry 
• Fish 
Non Heme iron:- 
• Leafy vegetables 
• Legumes 
• Beans 
• Cereals 
• Milk
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
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 % - Blood plasma as transferrin.
.
ROLE OF IRON IN THE BODY 
• Hematopoiesis. 
• Found in Hemoglobin and myoglobin. 
• Cytochrome P450 superfamily and catalase, which 
metabolize drugs and degrade hydrogen peroxide. 
• Conversion of blood sugar to energy. 
• Production of enzymes ,new cells, amino acids, 
hormones and neurotransmitters. 
• Proper immune system functioning. 
• Physical and mental growth.
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.
• 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.
Control of iron absorption 
Mucosal block theory
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
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.
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.
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.
REGULATION OF IRON 
Ferroportin 
FP 
Hc 
LEVELS 
• 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.
DEFICIENCY OF IRON 
CAUSES- 
chronic bleeding. 
1.excessive menstrual bleeding. 
2.GIT bleeding (ulcers, hemorrhoids, Ulcerative 
Colitis etc.). 
inadequate intake. 
substances (in diet or drugs) interfering with 
iron absorption. 
malabsorption syndromes. 
Inflammation.
SYMPTOMS 
anemia 
fatigue 
dizziness 
pallor 
hair loss 
irritability 
weakness 
brittle or grooved nails 
glossitis 
BRITTLE 
GROOVED 
NAILS 
GLOSSITIS
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
EFFECTS OF IRON 
OVERLOAD 
• Cardiac failure 
• Liver cirrhosis/fibrosis/cancer 
• Diabetes mellitus 
• Infertility 
• Growth failure
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
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

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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 % - Blood plasma as transferrin.
  • 5. .
  • 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. • Conversion 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.
  • 10. Control of iron absorption Mucosal block theory
  • 11. 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
  • 12. 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.
  • 13.
  • 14. 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.
  • 15. 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.
  • 16. REGULATION OF IRON Ferroportin FP Hc LEVELS • 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.
  • 17.
  • 18. DEFICIENCY OF IRON CAUSES- chronic bleeding. 1.excessive menstrual bleeding. 2.GIT bleeding (ulcers, hemorrhoids, Ulcerative Colitis etc.). inadequate intake. substances (in diet or drugs) interfering with iron absorption. malabsorption syndromes. Inflammation.
  • 19. SYMPTOMS anemia fatigue dizziness pallor hair loss irritability weakness brittle or grooved nails glossitis BRITTLE GROOVED NAILS GLOSSITIS
  • 20. 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
  • 21. EFFECTS OF IRON OVERLOAD • Cardiac failure • Liver cirrhosis/fibrosis/cancer • Diabetes mellitus • Infertility • Growth failure
  • 22.
  • 23. 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
  • 24. 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