Iron in Clinical Practice E-Book
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- Herausgeber: John Wiley & Sons
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Learn the tools for addressing a widespread public health issue with this practical guide
Iron deficiency and iron overload are among the most common health conditions encountered in the course of clinical practice, with the potential to produce a range of morbidities and increase overall mortality. However, these conditions are often under-recognized, resulting in unnecessary disease and loss of well-being. There is an urgent need to raise awareness among clinicians of the causes, effects and management of iron imbalance.
Iron in Clinical Practice meets this need with a brisk, practical guide to recognizing and treating both iron deficiency and iron overload in clinical settings. Edited by two Oxford haematologists and leading specialists in iron management, it covers major areas of medicine and surgery impacted by these disorders. The result is an essential resource for both beginning and experienced clinicians.
Iron in Clinical Practice readers will find:
- Introductory chapters outlining the role of iron in the body, its utilization and mechanisms of trafficking and distribution, and how these are impacted by disease.
- Coverage of a range of clinical settings across medicine, surgery and primary care.
- Illustrations, tables, and graphs throughout.
Iron in Clinical Practice is ideal for all health care practitioners of any specialty.
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Seitenzahl: 234
Veröffentlichungsjahr: 2025
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Table of Contents
Cover
Table of Contents
Title Page
Copyright Page
List of Contributors
Preface
About the Companion Website
Part 1: Introduction to Iron
1 An Introduction to Iron in the Body
Introduction
Iron in the Body
Essential Functions of Iron in the Body
Iron Deficiency
Iron Overload
Bibliography
2 Regulation of Iron Trafficking in the Body
Introduction
Hepcidin and Systemic Iron Homeostasis
Regulation of Hepcidin
Cellular Iron Homeostasis: Ferritin and Transferrin Receptor
Assessing Iron Status – How the Markers Used Relate to Underlying Biology
Bibliography
3 Iron and Immunity
Introduction
The Battle for Iron and the Concept of ‘Nutritional Immunity’
Therapeutic Interventions Harnessing Nutritional Immunity
Iron Status and Susceptibility to Infections
Bibliography
Part 2: Iron Deficiency
Part 2a: Assessment and Management of Iron Deficiency
4 Impact of Iron Deficiency on the Individual
Introduction
Symptoms and Signs of Iron Deficiency
Impact of Iron Deficiency on Specific At‐risk Groups
Other Clinical Situations Associated with Iron Deficiency
Conclusion
Bibliography
5 Assessment of Iron Deficiency
Introduction
Definitions
Ferritin Thresholds
Inflammation and Liver Disease
Additional Biomarkers
Red Cell Indices
Hepcidin Levels
Conclusion
Bibliography
6 Available Treatments for Iron Deficiency
Introduction
Oral Iron Supplementation
Administration of Oral Iron
Intravenous Iron Therapy
Potential Adverse Effects of Intravenous Iron
Individualising Treatment
Bibliography
Part 2b: Causes, Impact, Management and Prevention of Iron Deficiency in Clinical Specialties
7 Iron Deficiency in Primary Care
Introduction
Presentation of Iron Deficiency in Primary Care
The Main Causes of Iron Deficiency in Primary Care
The Diagnosis of Iron Deficiency in Primary Care
Further Investigations
Treatment of Iron Deficiency in Primary Care
Dietary Advice and Prevention of Future Iron Deficiency
Bibliography
8 Iron Deficiency in the Preoperative Patient
Introduction
Haemoglobin Thresholds
Causes of Iron Deficiency in the Surgical Setting
Laboratory Tests
Management of Preoperative Iron Deficiency
Iron Treatment
Postoperative Management
Conclusion
Bibliography
9 Iron Deficiency in Gastroenterology
Introduction
Gastrointestinal Causes of Iron Deficiency
Assessment of Iron Deficiency in Patients with Gastrointestinal Disease
Specific Gastrointestinal Investigations
Angiodysplasia
Treatment of Iron Deficiency in Patients with Gastrointestinal Disease
Bibliography
10 Iron Deficiency in Renal Medicine
Introduction
Types of Iron Used in Nephrology and Safety Considerations
Iron Use in Haemodialysis Patients
Iron Use in Non‐Dialysis‐Dependent Chronic Kidney Disease
Iron Use in Peritoneal Dialysis
Bibliography
11 Iron Deficiency in Cardiology
Introduction
Causes of Iron Deficiency in Heart Failure
Impact of Iron Deficiency in Heart Failure
Management of Iron Deficiency in Heart Failure
Diagnostic and Management Uncertainties in Individuals with Cardiac Disease
Current Iron Replacement Therapies
Bibliography
12 Iron Deficiency in Neurology
Introduction
Iron Utilisation in the Central Nervous System
Iron and Neurocognitive Development
Neurological Associations with Iron Deficiency
Recommendations for Management of Iron Deficiency with Neurological Symptoms
Conclusion
Bibliography
13 Iron Deficiency in Obstetrics
Introduction
The Maternal Effects of Iron Deficiency
Fetal Effects of Iron Deficiency
Defining Anaemia in Pregnancy
How Is Iron Deficiency Diagnosed in Pregnancy?
Indications for Intravenous Iron
Management of Postpartum Anaemia
Bibliography
14 Iron Deficiency in Gynaecology
Introduction
Causes of Heavy Menstrual Bleeding
Definition of Heavy Menstrual Bleeding
Prevention of Iron Deficiency in Gynaecology
Investigation of Heavy Menstrual Bleeding
Management of Heavy Menstrual Bleeding
Iron Deficiency and Iron Deficiency Anaemia in Gynaecology
Impact of Iron Deficiency in Gynaecology
Management of Iron Deficiency in Women with Gynaecological Bleeding
Bibliography
15 Iron Deficiency in Orthopaedics
Introduction
Diagnosis
Aetiology of Iron Deficiency
Preoperative Treatment of Iron Deficiency Anaemia
Patient Outcomes
Iron Deficiency Without Anaemia
Bibliography
16 Iron Deficiency in Intensive Care
Introduction
Iron Homeostasis in Critical Illness
Diagnosing Iron Deficiency in Critical Illness
Clinical Implications of Iron Deficiency in Intensive Care Unit
Patient Blood Management in Intensive Care
Intravenous Iron in Intensive Care
Concomitant Therapies for Anaemia Management in Intensive Care
Bibliography
17 Iron Deficiency in Medical Oncology
Introduction
Causes of Anaemia in Patients with Cancer
Diagnosis of Iron Deficiency in Patients with Cancer
Management of Anaemia in Patients with Cancer
Erythropoiesis Stimulating Agents
Blood Transfusion in Oncology
Prevention of Anaemia in Patients with Cancer
Implementation of Local Policy
Novel Anti‐anaemia Agents
Conclusion
Bibliography
Part 3: Iron Overload
Part 3a: Causes of Iron Overload
18 Transfusional Iron Overload
Introduction
The Causes of Iron Overload and Influencing Factors
Pathophysiology and Effects of Transfusional Iron Loading on Body Iron Distribution
Rates of Transfusional Iron Overloading and Distribution in Different Diseases
Consequences of Transfusional Iron Overload
Prevention of Transfusional Iron Overload
Bibliography
19 Haemochromatosis
Introduction
Pathogenesis
Frequency and Penetrance of
HFE
‐Related Haemochromatosis
Diagnosis
Treatment and Prevention
Bibliography
20 Ineffective Erythropoiesis
Introduction
Erythropoiesis
The Role of Erythropoietin and Iron
Ferrokinetic Studies
Erythroferrone
Bibliography
Part 3b: Effects of Iron Overload on Body Organs
21 Iron Overload in the Heart
Iron and the Heart
Cardiac Iron Regulation
Iron Overload
Clinical Presentations and Their Management
Assessment of Cardiac Iron
Long‐Term Management and Prevention
Bibliography
22 Iron Overload and the Liver
Introduction
Histological Patterns of Hepatic Iron Overload
Pathophysiology of Hepatic Damage Secondary to Iron Overload
Assessment of Hepatic Iron Overload
Bibliography
23 Impact of Iron Overload on the Endocrine System
Introduction
Diabetes Mellitus
Reproductive Endocrinology
Growth and Bone Health
Adrenal Function
Summary
Bibliography
24 Iron Overload and the Musculoskeletal System
Introduction
Osteoporosis and Fracture Risk
Osteoarthritis
Calcium Pyrophosphate Deposition Disease
Management of Iron Overload in the Joints
Bibliography
Part 3c: Assessment and Management of Iron Overload
25 Assessment of Iron Overload
Introduction
Awareness of Potential Causes
Assessment of Transfusional Iron Overload
Role of Serum Ferritin and Iron Studies in Assessing Iron Overload
Imaging in Iron Overload
Monitoring Requirements for At‐risk Patients
Bibliography
26 Management of Iron Overload
Introduction
Iron Chelation Therapy
Indications for Iron Chelation Therapy
Administration of Iron Chelation Therapy
Combination Chelation Therapy
Calculation of ROIL Adults
Calculation of ROIL in Paediatric
Practical Prescribing Tips
Dose Adjustments for Comorbidities
Emerging Novel Therapies
Bibliography
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Distribution of iron in the body.
Chapter 4
Table 4.1 Reported symptoms in patients with iron deficiency with or withou...
Chapter 5
Table 5.1 Laboratory tests for ID in adults.
Chapter 6
Table 6.1 Commonly used oral iron supplements.
Table 6.2 Administration of oral iron.
Table 6.3 Intravenous iron formulations in common use.
Chapter 7
Table 7.1 Causes of iron deficiency presenting in primary care.
Chapter 9
Table 9.1 Common gastrointestinal causes of iron deficiency.
Chapter 11
Table 11.1 Causes underpinning high prevalence of ID in HF patients.
Chapter 13
Table 13.1 Risk factors for iron deficiency in pregnancy.
Chapter 14
Table 14.1 Risks for iron deficiency in gynaecology.
Chapter 16
Table 16.1 Definitions, laboratory characteristics and potential treatment s...
Chapter 17
Table 17.1 Causes, presentation and management of iron deficiency in oncolo...
Chapter 18
Table 18.1 Conditions at risk of transfusional iron overload.
Chapter 19
Table 19.1 Haemochromatosis (HC) classification, related genes, mode of tra...
Chapter 21
Table 21.1 Principles of successful management of cardiac complications.
Chapter 23
Table 23.1 Assessment of endocrine dysfunction in individuals with iron ove...
Chapter 25
Table 25.1 Conditions that may lead to iron overload, through ineffective e...
Table 25.2 Clinical interpretation of liver and cardiac iron overload by MR...
Table 25.3 Monitoring of individuals at risk of iron overload.
Chapter 26
Table 26.1 Available chelation regimens.
Table 26.2 Iron chelation regimens with monotherapy options.
Table 26.3 Iron chelation regimens with combination options.
Table 26.4 Optimal iron chelation according to age: current recommendations...
Table 26.5 The necessary frequency of monitoring before and during iron che...
List of Illustrations
Chapter 1
Figure 1.1 Iron‐containing proteins.
Figure 1.2 Iron utilisation.
Figure 1.3 Stages of red cell maturation where iron is utilised for haem syn...
Figure 1.4 Iron requirements in the nervous system. DAT, dopamine transporte...
Figure 1.5 Release of unpaired electrons (free radicals) during transition b...
Chapter 2
Figure 2.1 Overview of the regulation of ferroportin and iron trafficking by...
Figure 2.2 Control of hepcidin synthesis and cellular iron uptake mechanisms...
Figure 2.3 The IRP‐IRE system. During iron deficient conditions, iron respon...
Chapter 3
Figure 3.1 Hepcidin has an indirect antimicrobial activity by reducing iron ...
Figure 3.2 Beyond haemoglobin: iron is essential for many vital functions.
Figure 3.3 How common iron disorders can influence immune function and susce...
Chapter 4
Figure 4.1 Progressive stages of iron depletion.
Figure 4.2 Biological changes through the stages of iron depletion.
Chapter 5
Figure 5.1 Adequacy of body iron stores in various forms of ID and IDA.
Figure 5.2 Biomarkers in diagnosis and monitoring of ID. In the absence of i...
Figure 5.3 Alterations in biochemical and haematological parameters at diffe...
Chapter 7
Figure 7.1 Clinical signs of iron deficiency: angular cheilitis, glossitis a...
Figure 7.2 Approach to diagnosis of iron deficiency in primary care. RCC, re...
Chapter 8
Figure 8.1 Centre for Perioperative Care guideline for the management of ana...
Chapter 9
Figure 9.1 Histopathological image showing villous atrophy (triangle), intra...
Figure 9.2 Endoscopic image of gastric antral vascular ectasia (GAVE).
Figure 9.3 Endoscopic image of a bleeding duodenal Dieulafoy’s lesion.
Figure 9.4 Endoscopic image of an ascending colon malignancy.
Figure 9.5 Endoscopic image of rectal cancer.
Figure 9.6 Video capsule endoscopic image of small bowel angiodysplasia.
Figure 9.7 Flowchart for the investigation and management of IDA in gastroen...
Chapter 10
Figure 10.1 Hypophosphatemia and bone disorder syndrome. Increased FGF23 cau...
Figure 10.2 Results of the PIVOTAL study showing reduced mortality and major...
Figure 10.3 High levels of hepcidin produced by the liver, “lock” the iron i...
Figure 10.4 A randomised trial of intravenous iron isomaltoside versus oral ...
Chapter 11
Figure 11.1 Potential mechanisms for the detrimental effect of ID in HF pati...
Figure 11.2 Potential impact of inflammation and hepcidin on fate of iron fr...
Chapter 12
Figure 12.1 Iron crosses the endothelial cells (ECs) of the blood–brain barr...
Chapter 13
Figure 13.1 Iron requirements in pregnancy and the negative iron spiral in f...
Figure 13.2 A. Maternal hepcidin concentrations are decreased in the second ...
Figure 13.3 Blood volume changes in pregnancy.
Chapter 14
Figure 14.1 Fibroids.
Figure 14.2 Hormonal management of heavy menstrual bleeding.
Figure 14.3 Heavy menstrual bleeding treatment map. LNG‐IUS, levonorgestrel ...
Chapter 15
Figure 15.1 Pillars of patient blood management in orthopaedic surgery.
Chapter 16
Figure 16.1 Iron homeostasis in critically ill patients.
Figure 16.2 Complications of altered iron status in critically ill patients....
Chapter 17
Figure 17.1 Local policy for management of anaemia in patients with cancer....
Chapter 18
Figure 18.1 Distribution of iron overload. NTBI – non‐transferrin‐bound iron...
Figure 18.2 Pathological mechanisms of iron overload and toxicity. Iron exce...
Chapter 19
Figure 19.1 Hepcidin regulation by iron in hepatocytes. Increase in transfer...
Figure 19.2 Prevalence of the p.C282Y risk allele for haemochromatosis in Eu...
Chapter 20
Figure 20.1 An erythroblastic island. X400 image of a normal bone marrow ery...
Figure 20.2 Ineffective erythropoiesis. A comparison of normal erythropoiesi...
Chapter 21
Figure 21.1 A myocardial biopsy, obtained with permissions, from a patient w...
Figure 21.2 The UK thalassaemia cohort, showing deaths in intervals of 5 yea...
Chapter 22
Figure 22.1 Patterns of hepatic iron accumulation, with Perls’ Prussian blue...
Figure 22.2 Intercellular pathways in fibrosis development.
Chapter 23
Figure 23.1 The multiple organs involved in the pathogenesis of diabetes in ...
Figure 23.2 Proposed hypothalamicpituitary gonadal axis impairment in female...
Chapter 24
Figure 24.1 Iron overload and bone health.
Figure 24.2 Metacarpal hook osteophytes in hereditary haemochromatosis.
Guide
Cover Page
Table of Contents
Title Page
Copyright Page
List of Contributors
Preface
About the Companion Website
Begin Reading
Index
Wiley End User License Agreement
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Iron in Clinical Practice
Edited by
Sue Pavord
Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Noemi Roy
Oxford University Hospitals NHS Foundation Trust, Oxford, UK
This edition first published 2025© 2025 John Wiley & Sons Ltd
All rights reserved, including rights for text and data mining and training of artificial technologies or similar technologies No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Sue Pavord and Noemi Roy to be identified as the authors of the editorial material in this work has been asserted in accordance with law.
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Library of Congress Cataloging‐in‐Publication Data applied for
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List of Contributors
Imo J. AkpanDepartment of Medicine, Division ofHaematology/Oncology, ColumbiaUniversity Irving Medical CenterNew York, NY, USA
Samah BabikerEvelina London Children's HospitalSt Thomas' HospitalLondon, UK
Fabiana BustiDepartment of Medicine, Sectionof Internal Medicine, University ofVerona ItalyVeneto Region Referral Center for IronDisorders and European ReferenceNetwork Center for Rare HematologicalDiseases “EuroBloodNet”
Subarna ChakravortyDepartment of Paediatric HaematologyKing’s College HospitalLondon, UK
Jeremy CobboldDepartment of Gastroenterology andHepatologyOxford University Hospitals NHSFoundation Trust, Oxford, UK
Hal DrakesmithMedical Research Council TranslationalImmune Discovery Unit, MRC WeatherallInstitute of Molecular Medicine, Universityof Oxford, John Radcliffe HospitalHeadington, Oxford, UK
Caroline R. EvansDepartment of Anaesthetics, Cardiffand Vale University HealthboardCardiff, UK
Ian GaleaClinical Neurosciences, Clinical andExperimental Sciences, Faculty ofMedicine, University of Southampton, UKWessex Neurological Centre, UniversityHospital Southampton NHS FoundationTrust, UK
Domenico GirelliDepartment of Medicine, Sectionof Internal Medicine, University ofVerona ItalyVeneto Region Referral Center for IronDisorders and European ReferenceNetwork Center for Rare HematologicalDiseases “EuroBloodNet”
Carmen JacobClinical Neurosciences, Clinical andExperimental Sciences, Faculty ofMedicine, University of Southampton, UKWessex Neurological Centre, UniversityHospital Southampton NHS FoundationTrust, UK
Kassim JavaidThe Botnar Centre, Nuffield OrthopaedicCentre, Oxford, UK
Philip A. KalraDepartment of Nephrology, Salford RoyalHospital, Northern Care Alliance NHSFoundation Trust, UK
Patrick Kyei‐MensahDepartment of Haematology, OxfordUniversity Hospitals NHS FoundationTrust, Oxford, UK
Samira Lakhal‐LittletonDepartment of Physiology, Anatomy andGenetics, University of OxfordOxford, UK
Miles LevyDepartment of Diabetes & EndocrinologyUniversity Hospitals of Leicester NHSTrust,Leicester, UK
Hanke L. MatlungSanquin Research andLandsteiner LaboratoryDepartment of Molecular HematologyAmsterdam, the Netherlands
David McCartneySchool of Medicine and BiomedicalSciences, Medical Sciences DivisionUniversity of Oxford Academic CentreJohn Radcliffe HospitalOxford, UK
Amy MorrisonDepartment of Diabetes & EndocrinologyUniversity Hospitals of Leicester NHSTrustLeicester, UK
Nurulamin M. NoorDepartment of GastroenterologyCambridge University Hospitals NHSFoundation Trust, Cambridge, UKDepartment of Medicine, University ofCambridge School of Clinical MedicineCambridge, UK
Antony PalmerDepartment of Surgery, Nuffield OrthopaedicHospital, Oxford University Hospitals NHSFoundation Trust, Oxford, UK
Sue PavordDepartment of Haematology, OxfordUniversity Hospitals NHS FoundationTrust, Oxford, UK
Paolo PolzellaDepartment of Haematology, OxfordUniversity Hospitals NHS Foundation TrustOxford, UK
John PorterDepartment of HaematologyUniversity College HospitalLondon, UK
Graca PortoHematology Serviço de Imuno‐hemoterapia, CHUdSA‐Centro HospitalarUniversitário de Santo AntónioPorto, Portugal
Noemi RoyDepartment of Haematology, OxfordUniversity Hospitals NHS FoundationTrust, Oxford, UK
Nandini SadasivamDepartment of HaematologyManchester Royal InfirmaryManchester, UK
Emma SaunsburyDepartment of Gastroenterology andHepatologyOxford University Hospitals NHSFoundation TrustOxford, UK
Akshay ShahNuffield Department of ClinicalNeurosciences, University of OxfordOxford University Hospitals NHSFoundation TrustOxford, UKDepartment of AnaesthesiaHammersmith HospitalImperial College Healthcare NHS TrustLondon, UK
Mohmmed Tauseef SharipDepartment of GastroenterologyCambridge University Hospitals NHSFoundation Trust, Cambridge, UK
Dorine W. SwinkelsSanquin Blood BankAmsterdam, the NetherlandsDepartment of Laboratory MedicineRadboud University Medical CenterNijmegen, the Netherlands
Megan TehMedical Research Council TranslationalImmune Discovery Unit, MRC WeatherallInstitute of Molecular Medicine, Universityof Oxford, John Radcliffe HospitalHeadington, Oxford, UK
Malcolm WalkerHatter Cardiovascular Institute, UniversityCollege London HospitalLondon, UK
Preface
Sue Pavord and Noemi Roy
Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
“It is the greatest happiness of the greatest number that is the measure of right and wrong.”
The utilitarian approach of Jeremy Bentham, who stated this in reference to morals and legislation, can be applied to medical practice.
Iron disorders are common. Effective management of them ensures fitness and resilience throughout an individual’s life cycle – the fetal and neonatal period, growth and development, educational years, work productivity, pregnancy, aging, medical disease, and surgery.
The provision of healthcare is increasingly challenged by the advancing age and progressive diversity of populations. Maintaining optimal health for as long as possible is crucial for individuals and their families.
Recognition and management of iron disorders is one of the best examples of preventative medicine and paramount for population health.
We developed this book to raise awareness of iron disorders which are highly prevalent, disabling, underdiagnosed, and undertreated.
The book aims to provide healthcare professionals with a comprehensive guide to the role of iron in the body, recognising and diagnosing iron disorders and implementing successful treatment strategies.
This book should serve as a valuable resource for improving knowledge and skills in managing iron deficiency and iron overload.
The book is based on the latest available evidence. There remain gaps in our knowledge, which will continue to be filled over the coming years.
We thank all the contributors who have given up their time to generously share their specific knowledge and expertise.
About the Companion Website
This book is accompanied by a companion website:
www.wiley.com/go/pavord/ironinclinicalpractice1e
The website includes:
MCQs
Part 1Introduction to Iron
1An Introduction to Iron in the Body
Sue Pavord and Noemi Roy
Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Introduction
Iron is the most common element on Earth. In the Earth’s crust it is the fourth most abundant element after oxygen, silicon and aluminium, being mainly deposited by meteorites in its metallic state. As life evolved, organisms selected from available elements for fundamental physiological processes, and iron has been utilised by every living organism and is essential for a multitude of biological functions.
Humans have evolved structures to bind iron as well as using free iron ions (Figure 1.1). Iron participates in vital metabolic processes of every body cell, including oxygen transport, catalytic enzyme activity, electron transport, deoxyribonucleic acid (DNA) synthesis and cell proliferation. Cellular iron is predominantly located in the mitochondria and endoplasmic reticulum. In humans, 2% of genes encode an iron protein, and these genes are more frequently associated with pathologies than all other human genes.
Iron in the Body
An average sized human body will contain about 4 g iron, an approximate concentration of 50 mg/kg. Table 1.1 shows a rough distribution of iron in the body.
The daily intake of iron from a balanced diet is around 2 mg. This equals the daily losses from sweat and shedding of epithelial cells such as skin and intestinal cells so that iron is maintained in a physiological range. Iron is conserved in the body by recycling, a function of the reticuloendothelial system.
When released into the plasma from intestinal cells (following absorption from the gut) and reticuloendothelial macrophages (from phagocytosis of senescent red cells), it is captured by transferrin and delivered to the tissues. The iron‐bound transferrin attaches to the transferrin receptor (TfR) on the surface of cells, and its iron is internalised into the cell. Once inside the cell, iron is transported to mitochondria for the synthesis of haem or iron–sulphur clusters, which are integral parts of several metalloproteins. Surplus iron is stored and detoxified in ferritin (Figure 1.2).
Figure 1.1 Iron‐containing proteins.
Table 1.1 Distribution of iron in the body.
Percentage of total body iron
Oxygen transport and storage
Haemoglobin
60–70%
Myoglobin
10%
Energy generation
Mitochondrial cytochromes of electron transport chain; elements of citric acid cycle
~1%
Key enzymatic processes
Cytochrome P450 and other metabolic pathways
Synthesis
Catecholamine, neurotransmitter, melanin and collagen synthesis
Immune cell function
Storage
Ferritin, haemosiderin
20–30%
Transport
Transferrin
<0.2%
Figure 1.2 Iron utilisation.
Essential Functions of Iron in the Body
Approximately 70% of the iron is used by the bone marrow to make haemoglobin (Hb). This is synthesised by erythroblasts, which show high expression of TfRs. The erythroblast matures into a reticulocyte and ultimately to an erythrocyte (Figure 1.3). Around 8% of the iron is used in myoglobin, another haemoprotein responsible for oxygen binding and transport but specific to cardiac and skeletal muscle.
Iron is also required as a cofactor for many non‐haem proteins, including catalase and peroxidase enzymes, which take part in oxygen metabolism, and cytochromes, which are involved in electron transport and mitochondrial respiration. These non‐haem iron‐containing proteins have crucial functions, as they are used in DNA synthesis, gene regulation, cell proliferation and differentiation, hormone synthesis and drug metabolism. In the brain and nervous system, iron is required for neurotransmitter synthesis, myelin synthesis and development and metabolism of brain cells (Figure 1.4). The blood–brain barrier modulates iron levels in the brain.
Genetic and acquired diseases of the tissues and organs involved in iron utilisation and recycling cause a dysregulation of the iron cycle and may lead to iron deficiency or excess. Both have a negative impact on health.
Iron Deficiency
Iron deficiency (ID) is a global health concern, affecting more than four billion people worldwide. It is the most common nutritional deficiency in low‐ and middle‐income countries and in high‐income countries.
According to World Health Organisation (WHO) statistics, ID anaemia affects 30% of the world population, 40% of all children aged 6–59 months, 37% of pregnant women and 30% of all women aged 15–49 years. Because of its very wide prevalence, ID imposes a considerable burden of morbidity on a significant proportion of the world population.
