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Iron deficiency (medicine)

Iron deficiency (medicine)

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Iron deficiency is one of the most common of the nutritional deficiencies. Iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 is present in all cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

s in the human body
Human body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...

, and has several vital functions. Examples include as a carrier of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 to the tissues from the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

s in the form of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

, as a transport medium for electrons within the cells in the form of cytochrome
Cytochrome
Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport.They are found either as monomeric proteins or as subunits of bigger enzymatic complexes that catalyze redox reactions....

s, and as an integral part of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

.

The direct consequence of iron deficiency is iron deficiency anemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...

. Children and pre-menopausal women are the groups most prone to the disease.

Total body iron averages approximately 3.8 g in men and 2.3 g in women. In blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

, iron is carried tightly bound to the protein transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

. There are several mechanisms that control human iron metabolism
Human iron metabolism
Human iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...

 and safeguard against iron deficiency. The main regulatory mechanism is situated in the gastrointestinal tract. When loss of iron is not sufficiently compensated by adequate intake of iron from the diet, a state of iron deficiency develops over time. When this state is uncorrected, it leads to iron deficiency anemia.

Causes

  • chronic bleeding (hemoglobin
    Hemoglobin
    Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

     contains iron)
    • excessive menstrual bleeding
    • non-menstrual bleeding
      Bleeding
      Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

    • bleeding from the gastrointestinal tract
      Gastrointestinal tract
      The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

       (ulcers
      Peptic ulcer
      A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...

      , hemorrhoid
      Hemorrhoid
      Hemorrhoids or haemorrhoids , are vascular structures in the anal canal which help with stool control. They become pathological or piles when swollen or inflamed. In their physiological state they act as a cushion composed of arterio-venous channels and connective tissue that aid the passage of...

      s, etc.)
    • rarely, laryngological bleeding or from the respiratory tract
      Respiratory tract
      In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...

  • inadequate intake (special diets low in dietary iron)
  • substances (in diet or drugs) interfering with iron absorption
  • malabsorption
    Malabsorption
    Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...

     syndromes
  • fever
    Fever
    Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

     where it is adaptive
    Evolutionary medicine
    Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory to understanding health and disease. It provides a complementary scientific approach to the present mechanistic explanations that dominate medical science, and particularly modern medical education...

     to control bacterial infection
  • blood donation

Though genetic defects causing iron deficiency have been studied in rodents, there are no known genetic disorders of human iron metabolism
Human iron metabolism
Human iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...

 that directly cause iron deficiency.

Symptoms


Symptoms of iron deficiency can occur even before the condition has progressed to iron deficiency anaemia.

Symptoms of iron deficiency are not unique to iron deficiency (i.e. not pathognomonic
Pathognomonic
Pathognomonic is a term, often used in medicine, that means characteristic for a particular disease. A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt...

). Iron is needed for many enzymes to function normally, so a wide range of symptoms may eventually emerge, either as the secondary result of the anemia, or as other primary results of iron deficiency. Symptoms of iron deficiency include:
  • fatigue
    Fatigue (physical)
    Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...

  • pallor
    Pallor
    Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

  • hair loss
  • irritability
    Irritability
    Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....

  • weakness
    Muscle weakness
    Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...

  • pica
    Pica (disorder)
    Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...

  • brittle or grooved nails
  • Plummer-Vinson syndrome
    Plummer-Vinson syndrome
    Plummer–Vinson syndrome , also called Paterson–Brown–Kelly syndrome or sideropenic dysphagia presents as a triad of dysphagia , glossitis, and iron deficiency anemia...

    : painful atrophy of the mucous membrane
    Mucous membrane
    The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

     covering the tongue
    Tongue
    The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...

    , the pharynx
    Pharynx
    The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...

     and the oesophagus
  • Impaired immune function
  • Pagophagia
    Pagophagia
    -Pagophagia:The compulsive eating of ice that is a common symptom of a lack of iron is also a form of the disorder Pica, the ingestion of unusual foods or substances. More often Pagophagia is related to women who may be pregnant or people who have iron deficiency anemia...

  • Restless Legs Syndrome
    Restless legs syndrome
    Restless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...


Likely lab test results in people with iron deficiency

  • A full blood count would likely reveal microcytic anemia
    Microcytic anemia
    Microcytic anemia is a generic term for any type of anemia characterized by small red blood cells. The normal mean corpuscular volume is 76-100 fL, with smaller cells as macrocytic....


  • Low serum ferritin
    Ferritin
    Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...

     *see below
  • Low serum iron
    Serum iron
    Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin. Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause anemia and other problems....

  • High TIBC (total iron binding capacity)
  • It is possible that the fecal occult blood
    Fecal occult blood
    Fecal occult blood refers to blood in the feces that is not visibly apparent. A fecal occult blood test checks for hidden blood in the stool...

     test might be positive, if iron deficiency is the result of gastrointestinal bleeding
    Gastrointestinal bleeding
    Gastrointestinal bleeding or gastrointestinal hemorrhage describes every form of hemorrhage in the gastrointestinal tract, from the pharynx to the rectum. It has diverse causes, and a medical history, as well as physical examination, generally distinguishes between the main forms...

    .


As always, laboratory values have to be interpreted with the lab's reference values in mind and considering all aspects of the individual clinical situation.

Serum ferritin can be elevated in inflammatory conditions and so a normal serum ferritin may not always exclude iron deficiency.

Consequences


Continued iron deficiency may progress to anemia and worsening fatigue. Thrombocytosis
Thrombocytosis
Thrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive...

, or an elevated platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days...

 count, can also result. A lack of sufficient iron levels in the blood is a reason that some people cannot donate blood.

Treatment


Before commencing treatment, there should be definitive diagnosis
of the underlying cause for iron deficiency. This is particularly the case in older patients, who are most susceptible to colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

 and the gastrointestinal bleeding it often causes. In adults, 60% of patients with iron deficiency anemia may have underlying gastrointestinal disorders leading to chronic blood loss.
It is likely that the cause of the iron deficiency will need treatment as well.

Upon diagnosis, the condition can be treated with iron supplements
Iron supplements
Iron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....

, e.g. in the form of ferrous sulfate, ferrous gluconate, or amino acid chelate tablets. Recent research suggests the replacement dose of iron, at least in the elderly with iron deficiency, may be as little as 15 mg per day of elemental iron.

Food sources of iron


Mild iron deficiency can be prevented or corrected by eating iron-rich foods. Because iron is a requirement for most plants and animals, a wide range of foods provide iron. Good sources of dietary iron include red meat
Red meat
Red meat in traditional culinary terminology is meat which is red when raw and not white when cooked. In the nutritional sciences, red meat includes all mammal meat. Red meat includes the meat of most adult mammals and some fowl ....

, poultry
Poultry
Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...

, insects, lentil
Lentil
The lentil is an edible pulse. It is a bushy annual plant of the legume family, grown for its lens-shaped seeds...

s, bean
Bean
Bean is a common name for large plant seeds of several genera of the family Fabaceae used for human food or animal feed....

s, leafy vegetables, pistachio
Pistachio
The pistachio, Pistacia vera in the Anacardiaceae family, is a small tree originally from Persia , which now can also be found in regions of Syria, Lebanon, Turkey, Greece, Kyrgyzstan, Turkmenistan, India, Pakistan, Egypt, Sicily and possibly Afghanistan , as well as in the United States,...

s, tofu
Tofu
is a food made by coagulating soy milk and then pressing the resulting curds into soft white blocks. It is part of East Asian and Southeast Asian cuisine such as Chinese, Japanese, Korean, Indonesian, Vietnamese, and others. There are many different varieties of tofu, including fresh tofu and tofu...

, fortified bread, and fortified breakfast cereals.

Iron from different foods is absorbed and processed differently by the body; for instance, iron in meat (heme iron source) is more easily broken down and absorbed than iron in grains and vegetables ("non-heme" iron source), but heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

/hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

 from red meat has effects which may increase the likelihood of colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

. Minerals and chemicals in one type of food may inhibit absorption of iron from another type of food eaten at the same time. For example, oxalate
Oxalate
Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...

s and phytic acid
Phytic acid
Phytic acid is the principal storage form of phosphorus in many plant tissues, especially bran and seeds. Phytate is not digestible to humans or nonruminant animals, however, so it is not a source of either inositol or phosphate if eaten directly...

 form insoluble complexes which bind iron in the gut before it can be absorbed.

Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, vegetarians and vegans should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry. Legumes and dark-green leafy vegetables like broccoli
Broccoli
Broccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage"....

, kale
Kale
Kale is very high in beta carotene, vitamin K, vitamin C, lutein, zeaxanthin, and reasonably rich in calcium. Kale, as with broccoli and other brassicas, contains sulforaphane , a chemical with potent anti-cancer properties. Boiling decreases the level of sulforaphane; however, steaming,...

 and oriental greens are especially good sources of iron for vegetarians and vegans. However, spinach
Spinach
Spinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant , which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions...

 and Swiss chard contain oxalates which bind iron making it almost entirely unavailable for absorption. Iron from nonheme sources is more readily absorbed if consumed with foods that contain either heme-bound iron or vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

. This is due to a hypothesised "meat factor" which enhances iron absorption.

Iron deficiency can have serious health consequences that diet may not be able to quickly correct, and iron supplementation is often necessary if the iron deficiency has become symptomatic.

Bioavailability and bacterial infection


Iron is needed for bacterial growth
Bacterial growth
250px|right|thumb|Growth is shown as L = log where numbers is the number of colony forming units per ml, versus T Bacterial growth is the division of one bacterium into two daughter cells in a process called binary fission. Providing no mutational event occurs the resulting daughter cells are...

 making its bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

 an important factor in controlling infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

. Blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 as a result carries iron tightly bound to transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

, and only releases it to cells with appropriate cell markers thus preventing its access to bacteria. Between 15 and 20 percent of the protein content in human milk consists of lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...

 that binds iron. As a comparison, in cow's milk, this is only 2 percent. As a result, breast fed babies have fewer infections. Lactoferrin is also concentrated in tears, saliva and at wounds to bind iron to limit bacterial growth. Egg white
Egg white
Egg white is the common name for the clear liquid contained within an egg. In chickens it is formed from the layers of secretions of the anterior section of the hen's oviduct during the passage of the egg. It forms around either fertilized or unfertilized egg yolks...

 contains 12% conalbumin
Conalbumin
Conalbumin is one of the two major types of albumin found in egg white. It comprises approximately 13% of albumen . Biologically, conalbumin isolates and sequesters metallic contaminants in the egg white....

 to withhold it from bacteria that get through the egg shell (for this reason prior to antibiotics, egg white was used to treat infections).

To reduce bacterial growth, plasma concentrations of iron are lowered in fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, and following surgery after open wounds where it acts as a protection against infection. Reflecting this link between iron bioavailability and bacterial growth, the taking of iron supplements
Iron supplements
Iron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....

can increase the risk of infection. A moderate iron deficiency, in contrast, can provide protection against acute infection.

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