IRON IN HEALTH AND DISEASE

Surah 57. Al-Hadid (The Iron) Aya: 25

We have indeed sent Our messengers with clear evidences and sent down with them the Scripture and the balance that the people may maintain (their affairs) in justice. And we sent down iron, where in is great military might and benefits for the people, and so that Allah may make evident those who support Him and His messengers unseen. Indeed, Allah is powerful and Exalted in Might.

Surah 57. Al-Hadid (The Iron) Aya: 25

Learning Objectives Distribution Daily Requirements Dietary sources Important functions Absorption & Metabolism Deficiency diseases

Introduction It is a well establish fact now that: deficiency or over exposure to various elements has noticeable effects on human health. Element’s effect is determined by many factors, including absorption, metabolism, and its interaction with other processes. Iron is an essential element for almost all living organisms. It participates in a wide variety of metabolic processes, including O2 and CO2 transport, DNA synthesis, and electron transport.

However, Iron can form free radicals, its concentration in body tissues must be tightly regulated . In excessive amounts, it can lead to tissue damage. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations. Ranging from anemia to iron overload, and possibly to neurodegenerative diseases.

IRON Called by Egyptians as “Heavenly metal”. Used as medicine around 1500 B.C. for the treatment of parasitic infection and a variety of other ailments. Quran describes it as a means of power. One of the most plentiful elements on earth. 5% of earth crust, still its deficiency a common health problem

IRON 18th Century: presence was demonstrated in animal tissues and blood. 20th Century: Much learnt about iron & its interaction with other elements.

At. No. 26 IRON At. Mass 56

IRON ( Al-Hadeed) Fe Aya No. 25 Sura No. 57

DISTRIBUTION 4 grams of Fe ,on an average in human body 3 grams in active or functional form and 1 gram in storage or transport form.

Distribution of Iron in human body Hemoglobin 66% Myoglobin 03% Other body cells 05% Enzymes 01% Ferritin (store) 25%

Recommended Dietary Allowance Infants 0 – 0.5 = 10 mg 0.5 – 1.0 = 15 mg Children 1 – 3 = 15 mg 4 – 6 = 10 mg 7 – 10 = 10 mg

Iron RDA Age Male Female 11 – 14 18 mg 15 – 18 19 – 22 10 mg 23 – 50 51 +

Major Dietary sources Red meat, Liver and Eggs Green Vegetables and , Cereals Apple, Nuts, Peaches and Dry fruits Iron from cooking utensils, made of iron

FUNCTIONS Essential elements in the daily diet. Vital role in O2 transport and energy production. Exclusively involved in the uptake and release of O2 at cellular level.

FUNCTIONS Active part is mostly in Porphyrin and forms an integral part of Hb and Myoglobin, In RBCs enzymes cytochrome, oxidase, catalase and peroxidases .

FUNCTIONS Myoglobin works on similar principle but performs in muscles only.

FUNCTIONS Shuttles O2 from lungs to all other tissues and CO2 back from tissues to lungs. Ability of Hb molecule to take up O2 and release CO2, is dependent on presence of Fe in Hb. Without Fe, the Hb. molecule cannot perform this function. The cytochrome enzyme system functions in energy production.

Absorption and Metabolism

METABOLISM Fe++ is absorbed from intestinal lumen into the cells of intestinal mucosa. Here Fe++ is oxidized to Fe+++ Combines with proteins Apoferritin. Iron – protein complex, Ferritin and stored.

EXCRETION Iron is unique among mineral elements. There is no physiologic mechanism for regulating its increase or decrease excretion. Balance is mainly controlled at the site of intestinal absorption.

that increase or decrease the availability of iron for absorption. Iron Absorption Absorption is influenced by the amount already present in the diet / food that increase or decrease the availability of iron for absorption. Primary regulator of iron homeostasis 1-50% of iron is absorbed. If body needs more iron, it increases amount of “transferrin” an iron carrying protein. Iron can also be stored in another protein called “ferritin”

Iron Absorption

Enterocyte Gut ABSORPTION OF IRON Fe+++ Ferritin Fe++ Tf-Fe+++ Fe++ Haem Tf

BODY IRON CYCLING

Absorption Heme iron is better absorbed than non heme iron During states of iron balance, about 10% of dietary iron is absorbed Figure can increase by 2 or 3 times, during periods of iron deficiency

METABOLISM When iron is needed by the body, Ferritin gives up its iron to the blood stream. Fe+++ iron is reduced within the mucosal cell to Fe++ form and released. The apoferritin in the mucosal cell can then combine with dietary iron absorbed in the intestine. If all the mucosal cells are saturated, no further absorption.

METABOLISM Most of iron in blood stream is utilized by bone marrow to synthesize Hb. Some is used by other tissue in the formation of enzyme

Factors affecting Iron Absorption Absorbed through intestinal mucosa, only when needed Ferrous (Fe++) is better absorbed than Fe+++ (Ferric) Better absorbed in Acidic medium, by virtue of conversion of ferric to ferrous state.

Absorption Absorption increase with need: Period of rapid growth in infancy. Childhood and adolescence During pregnancy, As a result of blood loss and At high attitude.

Factors Absorption is more efficient in presence of Vit C, and other reducing substances Vitamin C and fructose forms soluble complexes with iron and therefore better absorbed.

High fiber in diet – decrease iron absorption Tea can also inhibit the absorption of non heme iron Phosphate, Oxalates, Phytates forms insoluble complexes with iron, preventing absorption.

IRON DEFICIENCY Hypo chromic anemia: No of RBCs are either normal or reduced Amount of circulating Hb is reduced In each RBC the Hb. content fall Hb low, oxygen carrying capacity is reduced

IRON REQUIREMENTS Due to efficient conservation and reutilization in the body daily physiologic requirement is small. Healthy man loses about 0.5-1 mg/day iron, while women lose about 1-1.8 mg/day 10% of average available dietary iron is absorbed which comes to 5-10 mg/day required for men and 10-18 mg/day required for women

IRON REQUIREMENTS Pregnancy increase iron daily need by 3.5 mg/day To be taken as iron supplement and not diet 30 – 60 mg/day Lactation iron losses are 0.5 – 1.0 mg/day Continuous Supplementation needed for 2 – 3 month after delivery

IRON DEFICIENCY Commonest cause of anaemia worldwide Cause of chronic ill health May indicate the presence of important underlying disease eg. blood loss from tumour

CLINICAL FEATURES (Symptoms) Dizziness Headache Weakness Fatigue

CLINICAL FEATURES (signs) Pallor Glossitis Angular cheilosis and koilonychia. Koilonychia Glossitis

CLINICAL FEATURES OF IRON DEFICIENCY Angular Cheilosis or Stomatitis                                         

Hypochromic microcytic red cells

Iron deficiency develops Poor diet Chronic blood loss or both Intestinal parasite Bleeding Hemorrhoids Peptic Ulcer Heavy menstrual losses Closed space pregnancy Insufficient proteins Insufficient calories B – vitamins. / Ascorbic acid

Common situation where Iron Intake is inadequate. During infancy: Low iron content of milk Fe stores at birth which are usually sufficient only for first 6 months. During rapid growth in child hood and adolescences: Because of the need of expanding iron stores.

Common situation where Iron Intake is inadequate. During reproductive period: Menstrual losses During pregnancy, because of increased: Maternal blood volume Demands of the fetus and placenta Blood losses during child birth.

Iron overload Total amount of Fe in body can be increased by Excessive intake. Taking care of Abnormalities in iron absorption. Parenteral administration of iron. Overload iron by food alone  very difficult because of intestinal mucosal absorption.

Deposition of iron in the parenchymal cells of the liver. Toxic intakes of iron reported in children and adults ingesting medicinal iron supplements. Lethal dose for Young Child = 3 grams Adult = 200 – 250 mg/kg BW. Overload can also be caused by defect in intestinal mucosa. (Hemochromatosis) Deposition of iron in the parenchymal cells of the liver.

BONE MARROW FILM STAINED FOR HAEMOSIDERIN

Advance stage Graying pigmentation of skin Poor liver function Liver enlargement and scaring Pancreatic infiltration and resultant diabetes. Myocardial disease resulting in Heart failure.

Things you need to know about Laboratory Testing for Iron Status Serum ferritin most useful test Low serum ferritin , a proof that patient is iron deficient Normal serum ferritin does not always rule out iron deficiency Certain conditions raise ferritin for reasons unrelated to iron status

DIFFERENTIAL DIAGNOSIS: IRON DEFICIENCY ANAEMIA

LABORATORY DIAGNOSIS Elevated % transferrin saturation Increased serum ferritin Genetic testing for mutations of HFE gene Evidence parenchymal iron overload on liver biopsy Amount of iron removed by venesection

WHEN DOES IRON BECOME A PROBLEM? Normally 3-5 grams of iron in the body. Tissue damage when total body iron is 7 – 15 g Total body iron is also increased to variable ammounts at baseline by the ineffective hematopoiesis of MDS which leads to suppressed hepcidin: which leads to excessive intestinal absorption of iron and recycling of catabolic iron from the RES cells 57