IDA Lecture - Dr Madu.pdf

Iron Deficiency Anaemia Anazoeze Madu FMCPath  IRON IN NATURE  Iron is among the abundant minerals on earth.  O f t h e 8 7 e l e m e n t s i n t h e e a r t h’s c r u s t , I r o n constitutes 5.6% and ranks fourth behind Oxygen (46.4%), Silicon (28.4%) and Aluminum (8.3%)....

Iron Deficiency Anaemia Anazoeze Madu FMCPath  IRON IN NATURE  Iron is among the abundant minerals on earth.  O f t h e 8 7 e l e m e n t s i n t h e e a r t h’s c r u s t , I r o n constitutes 5.6% and ranks fourth behind Oxygen (46.4%), Silicon (28.4%) and Aluminum (8.3%).  In soil, Iron is 100 times more than Ca, Na & Mg and 1 0 0 0 t i m e s m o re t han Z i nc and 1 0 0 , 0 0 0 times more than Iodine.  Iron deficiency  I r o n d e f ic i e n c y i s t h e m o s t c o m m o n m i c r o n u t r i e n t d e f ic i e n c y i n t h e w o r l d affecting 1.3 billion people i.e. 24% of the world population.  In comparison only 275 million are iodine d e f ic i e n t an d 4 5 m i l l i o n c h i l d r e n b e l o w age 5 years are Vitamin A deficient.  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  Iron deficiency Iron deficiency can range from sub-clinical state to severe iron deficiency anemia. Different stages are identified by clinical findings & lab tests. Anemia is defined as a hemoglobin below the 5th percentile of healthy population. Most studies showed this cutoff point to be around 11 g/dl (-2SD below the mean).  At risk Groups Infants Under 5 children Children of school age Women of child bearing age  Prevalence of ID  Region 0-4yr 5-12yr Women  South Asia 56% 50% 58%  Africa 56% 49% 44%  Latin Am 26% 26% 17%  Gulf Arabs 40% 36% 38%  Developed 12% 7% 11%  World 43% 37% 35%  Etiology Inadequate intake of iron & of food, which enhances iron absorption. High intake of inhibitors of iron absorption Hookworm infestation. Blood loss (heavy menses & gastro-intestinal bleeding use of aspirin & NSAID). High fer tility rate and menorrhagia in women. Low iron stores in newborns.  Dietary Iron  There are 2 types of iron in the diet; haem iron and non-haem iron  Haem iron is present in Hb containing animal food like meat, liver & spleen  Non-haem iron is obtained from cereals, vegetables & beans  Milk is a poor source of iron, hence breast -fed babies need iron supplements  Iron Absorption Haem iron is not affected by ingestion of other food items. It has constant absorption rate of 20-30% which is little affected by the iron balance of the subject. The haem molecule is absorbed intact and the iron is released in the mucosal cells.  Iron Absorption (2)  T h e ab s o r p ti o n o f n o n - h ae m i r o n v ar i e s g r e atl y fr om 2 % to 1 0 0 % b e c au s e i t i s strongly influenced by: The iron status of the body The solubility of iron salts Integrity of gut mucosa Presence of absorption inhibitors or facilitators  Inhibitors of iron absorption  Food with polyphenol compounds Cereals like sorghum & oats Vegetables such as spinach and spices Beverages like tea, coffee, cocoa and wine. A s i n g l e c u p o f t e a t a k e n w i t h m e a l re d u c e s iron absorption by up to 11%.  Other inhibitors  F o o d c o n t a i n i n g p h y t i c a c i d i. e. B ra n , c e r e al s l i k e w h e at, r i c e , m ai z e & b ar e l y. L e g u m e s l i k e s o y a b e an s , b l ac k b e an s & peas.  C o w ’s m i l k d u e t o i t s h i g h c a l c i u m & casein contents.  Inhibition-how? The dietary phenols & phytic acids compounds bind with iron decreasing free iron in the gut & forming complexes that are not absorbed.  Cereal milling to remove bran reduces its phytic acid content by 50%.  Promoters of Iron Absorption  Foods containing ascorbic acid like citrus fruits, broccoli & other dark green vegetables because ascorbic acid reduces iron from ferric to ferrous forms, which increases its absorption.  Fo o d s c o nt a i ni ng m u sc l e p ro t e i n e nh a nc e i ro n ab sorp tion due to the ef f ec t of c ysteine c o ntai ni ng p e p ti d e s re l e ase d f ro m p ar ti al l y d i g e st e d m e a t , w h i c h re d u c e s f e rri c t o f e rro u s salts and form soluble iron complexes.  Iron absorption Some fruits inhibit the absorption of iron although they are rich in ascorbic acid because of their high phenol content e.g strawberry, banana and melon. Food fermentation aids iron absorption by reducing the phytate content of diet  Iron transport Transferrin is the major protein responsible for transpor ting iron in the body. Transferrin receptors, located in almost all cells of the body, can bind two molecules of transferrin. Both transferrin concentration & transferrin receptors are impor tant in assessing iron status.  Storage of iron Tissues with higher requirement for iron ( bone marrow, liver & placenta) contain more transferrin receptors. Once in tissues, iron is stored as ferritin & hemosiderin compounds, which are present in the liver, RE cells & bone marrow. The amount of iron in the storage compartment depends on iron balance (positive or negative). Ferritin level reflects amount of stored iron in the body & is important in assessing ID. Iron cycle in the body  Role of iron in the body Iron have several vital functions  Carrier of oxygen from lung to tissues  Transpor t of electrons within cells  Co-factor of essential enzymatic reactions: Neurotransmission Synthesis of steroid hormones Synthesis of bile salts Detoxification processes in the liver LOOK FOR THE CAUSE OF IRON DEFICIENCY  Causes of iron deficiency Increased physiologic demand eg. pregnancy, lactation, rapid growth Blood loss from GI tract, uterus, haemoglobinuria Malabsorption Diet colon cancer Evolution of iron deficiency anaemia Earliest stage : depletion of body iron stores only “Biochemical” iron deficiency without anaemia Iron deficiency anaemia  Clinical features iron deficiency Symptoms eg. fatigue, dizziness, headache Signs eg. pallor, glossitis, angular cheilosis, koilonychia, Plummer Vinson syndrome, brittle hair and nails Koilonychia Glossitis CLINICAL FEATURES OF IRON DEFICIENCY Plummer Vinson Syndrome : Angular Cheilosis Oesophageal Web or Stomatitis Laboratory diagnosis: Iron deficiency Microcytic hypochromic anaemia Often pencil cells and target cells on blood film Decreased serum ferritin Decreased serum iron, increased TIBC, decreased % transferrin saturation Low Marrow stainable Iron (Perls stain) Absent bone marrow haemosiderin : (rarely required for diagnosis )  LAB FINDINGS IN IDA Microcytic hypochromic anaemia Low Hb level (< 11.0 g/dl) Low MCV, MCH, MCHC Low serum ferritin Low retic count High RWD High iron binding capacity High erythrocyte protoporphyrin Differential diagnosis: Iron deficiency anaemia  Hypochromic microcytic red cells Pencil Cell Absent iron stores in bone marrow in iron deficiency Normal control Iron deficiency  Things you need to know about Laboratory Testing for Iron Status Serum ferritin most useful test Low serum ferritin cer tain proof patient iron deficient Normal serum ferritin does not always rule out iron deficiency Cer tain conditions raise ferritin for reasons unrelated to iron status Normal Blood Film Microcytes Hypochromia  Consequences of Iron Deficiency Increase maternal & fetal mortality. Increase risk of premature delivery and LBW. Learning disabilities & delayed psychomotor development. Reduced work capacity. Impaired immunity (high risk of infection). Inability to maintain body temperature. Associated risk of lead poisoning because of pica.  Principles of treatment Use oral iron ( not enteric coated tablets ) Replace iron deficit in total :  Restore haemoglobin and MCV to normal  Replenish iron stores Establish and treat the cause  Types of Iron Therapy Oral Formulations - Ferrous sulpahte ; best bioavailability, causes GI irriation. Contains highest qty of elemental Fe (66mg) - Ferrous fumarate: less bioavailable, better tolerated, less elemental Fe - Ferrous Gluconate - Iron Maltose: Better tolerated  Types of Iron Therapy Parenteral Formulations Given only there is need rapidly replace Iron or very serious challenges with compliance - Intravenous Iron therapy (Imferon): given with IV 5% Dex. May cause anaphytlaxis and death. Give test dose slowly. Prepare emergency tray before commencing infusion. Intramuscular Iron (Jectofer): Causes dark patch on the skin. Give using the Z-method.  Treatment Aim 1. Continue Iron therapy till Hb returns to normal - First response is a clinical “feeling of well bei n g” - Next is the Reticulocyte count retuens to normal - Then last is the haemoglobin conc. 2. Continue treatment for another 6 weeks: To replenish the iron stores.  Management of IDA Blood transfusion if heart failure is eminent IV or IM iron in pregnant women Oral iron 3-5 mg Fe/kg/day Treat underlying cause Dietary education  Prevention of IDA  Dietary modification  F o o d f o r t i fic a t i o n  Iron supplementation  Prevention of IDA  Diet & nutrition education eat more fruits and vegetable no coffee or tea with meals programmes should be targeted to at risk groups reduce phytic content of cereals and legumes by fermentation  Prevention of IDA  Shor t term approach: supplementation with iron tablets.  Long-term approach: food fortification with iron either for the whole p o p u l a t i o n ( b l a n k e t f o r t i f ic a t i o n ) o r f o r specif ic target groups like infants. It requires no c oop eration from users unlike taking iron supplements.  FOOD FORTIFICATION  Iron compounds used in food for tification can be divided into 4 groups Freely water soluble (ferrous sulphate, gluconate, lactate & ferric ammonium citrate). Poorly water soluble (ferrous fumarate, succinate & saccharate). Water insoluble (ferric pyrophosphate, ferric orthophosphate & elemental iron). Experimental (sodium-iron EDTA & bovine Hb concentrate).  Which iron form to use?  The major factors governing the choice of iron compound include: Bioavailability Organoleptic problems Cost Safety  Ideally we should go for a safe, cheap, highly bioavailable iron, which causes no organoleptic side-effects  Which iron form to use? Freely water soluble iron are the most bio- available, but causes unacceptable colour & flavour change in many foods. Insoluble iron compounds are inert with no organoleptic effects but it is poorly absorbed Cost-wise elemental iron is the cheapest, ferrous sulphate costs 10 times more, but most expensive is EDTA Safety is of concern with EDTA & Bovine Hb only because of potential problems  Common Practice  Fe rro us sul p hate i s c o m m o nl y use d i n Rx & prevention of IDA because of good absorption & high bioavailability, but it has its drawbacks  GIT disturbances & staining of teeth are frequent  Effects on fortified foods may include: Fat oxidation & rancidity Colour changes Metallic taste Precipitation  C as e 1 28 yr old presented with progressive weakness,leg swelling and dyspnoea on exer tion. Her period lasts 7 days, comes in clots with 3-4 pad changes per day. Hb 6.1g/dL, WBC 4.2 x 109 /L, Platelet 303 x 109/L. How would you investigate? Most likely result? Treatment?  C as e 2 46 year old man with cancer of the duodenum had ileostomy and is fed via this site. Noted to have a Hb of 6.9g/dL. How would you inestigate? What is the most like aetiological cause? How will treat? IRON OVERLOAD  Effects of Iron Overload Iron overload Capacity of serum transferrin to bind iron is exceeded Non-transferrin-bound iron (NTBI) circulates in the plasma O2- + H2O2 O2 + OH- + HO Excess iron promotes the generation of free hydroxyl Insoluble iron complexes radicals, propagators of are deposited in body oxygen-related tissue tissues and end-organ damage toxicity occurs (Fenton Reaction) Cardiac Liver cirrhosis/ HS C D iabetes Growth Infertility failure fibrosis/cancer senescence mellitus failure When does Iron become a problem? Normally 2.5 – 3.5g of iron in the body. Tissue damage when total body iron is 7 – 15 g  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  Treatment and Prevention Phlebotomy until ferritin