Iron deficiency occurs when the intake and absorption of iron are insufficient to replenish the body’s loss. When total body iron stores are depleted, the hemoglobin levels fall. Ferritin is the major storage form of iron and holds the iron available for future use. It is made of a protein shell that encloses an iron core containing 4500 iron atoms. Hemosiderin is composed of aggregates of ferritin molecules that have partially lost their protein shells. It is a more stable but less accessible and soluble form of storage iron.
Iron depletion and iron deficiency
As iron stores become depleted, three phases occur sequentially:
(i) Initially, iron stores are depleted, but enough iron remains so that red cell production continues and hemoglobin values remain normal. Additionally, supply of iron to tissues remains normal. Ferritin levels are beginning to fall.
(ii) As iron levels continue to fall, tissues may become iron depleted, but there is still no anemia. At this level, ferritin levels are low, Tf levels are increased, Hb, MCV are within normal limits, but there may be a few hypochromic red cells.
(iii) Lastly, once iron stores are fully depleted, there is no longer sufficient iron to maintain red cell production, and anemia results. Cells become progressively hypochromic and microcytic. Other tissues may be affected by iron deficiency such as nails, tongue, etc.
Causes of iron deficiency
A. Causes of iron deficiency related to the GI tract
(i) GI blood loss must be considered in iron deficient men and post -menopausal women.
(ii) Colonoscopy, upper endoscopy are the beginning evaluation, and if negative, should prompt a capsule endoscopy
(iii) Iron malabsorption due to gastric bypass surgery for obesity (which removes parietal cells that produce HCl that contributes to the conversion of food iron Fe 3 + to Fe 2 + form for optimal absorption and bypasses the duodenum — the major site of iron absorption) is an increasingly common condition.
(iv) Celiacsprue is an uncommon cause of iron deficiency.
(V) Non – heme iron intake may be inadequate in vegetarians — especially since this form of iron is less -well absorbed than heme – iron found in meat. Iron deficiency is more common in vegans.
Esophagitis | Varices | Ulcers | Gastritis | Gastric antral vascular ectasia (GAVE syndrome, aka watermelon stomach) | Arteriovenous malformations | Polyps | Tumors | Inflammatory bowel disease |Parasitic infection | Meckel’s diverticulum | Milk – induced enteropathy (in infants) Gynecologic | Lactation |Bladder neoplasms |Epistaxis |Blood donation |Hemoglobinuria | Self – induced bleeding (auto – phlebotomy) | Pulmonary hemosiderosis | Hereditary hemorrhagic telangiectasia | Runner’s anemia | Iron loss through the urine in patients with chronic intravascular hemolysis
Causes of iron deficiency in infancy
(i) Inadequate iron stores at birth (usually due to iron deficiency in the mother). Prematurity also plays a role, since half of the infant’s iron stores are deposited in the last month of fetal life. Fetal – maternal hemorrhage is a third mechanism.
(ii) Inadequate iron in the diet:
1. The growing child needs 0.5 – 1 mg of iron daily which cannot be supplied by breast milk alone.
2. Whole cow’s milk increases intestinal blood loss in infants, and non – iron – fortified cow’s milk formula increases the likelihood of developing iron deficiency anemia.
Causes of iron deficiency in women of child – bearing age
(i) Iron loss through menstruation:
1. Monthly blood loss in normal women ranges from 10 – 180 mL.
2. Maximum iron in a normal diet (20 mg daily) can replace the iron in 60 mL of monthly menstrual blood.
3. Thus, many women teeter on the brink of iron deficiency and need only slight changes in the diet or a single pregnancy to become frankly anemic.
(ii) Iron loss in pregnancy and delivery:
1. With each pregnancy, a woman loses 500 – 700 mg of iron — 250 mg to the fetus, and the remainder in the placenta and through hemorrhage.
2. Pregnant women thus need additional iron intake of 20 – 30 mg/d.
3. Further iron is required during lactation.
Patients may be asymptomatic or present with signs/symptoms of anemia, including fatigue, weakness, pallor, palpitations, lightheadedness, headaches, tinnitus, exertional dyspnea.
- GI symptoms — abdominal pain from an ulcer, change in stools from a colon cancer.
- GYN symptoms — heavy menses, cramping from uterine fibroids.
- Glossitis (a smooth, waxy – appearing, red tongue, with atrophy of the papillae).
- Angular cheilitis (ulcerations or fissures at the corners of the mouth).
- Esophageal webs and strictures (a web of mucosa forms at the junction of the hypopharynx and esophagus and leads to dysphagia).
- Koilonychia (spooning of the nails, where the nails are concave instead of convex).
- Blue sclerae.
- Gastric atrophy.
- Pica (obsessive consumption of substances with no nutritional value, such as ice, starch, clay, paper).
- Restless leg syndrome — incidence higher in those with iron deficiency.
- Thrombocytosis — an elevated platelet count, for unexplained reasons.
- In children, iron deficiency can lead to impaired psychomotor and mental development.
Treatment of Iron deficiency
Oral replacement is the treatment of choice
Many forms, not all of which are equally tolerated by patients. Oral iron can cause GI upset (nausea and constipation) and it is wise to tell patients to take it with meals and to gradually increase the dose and frequency. Oral iron may also cause very dark and tarry stools. Oral iron absorption can be impaired by certain foods and drink (tea, dairy, grains) and by proton pump inhibitors.
Parenteral iron can be given if patient is intolerant of oral iron, or if there is iron malabsorption, or if there is considerable G.I. iron loss that cannot be maintained by oral replacement (e.g., bleeding small bowel angiodysplasia). There is a significant risk of anaphylaxis and other infusion – related reactions. Several commercial preparations are available consisting of iron sucrose, iron dextran, or sodium ferric gluconate complex.
1. Each unit of blood has 1 mg/mL of iron.
2. Each unit of blood will raise the hemoglobin value by about 1 g/dL.
3. In general, transfusion should be reserved for clinical signs or symptoms of cardiovascular compromise.