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Background
Iron deficiency is the most common nutritional disorder in the world. Iron is an essential element for humans, comprising from 2-6 grams in an adult female and male, respectively. The majority of iron (80%) is located within the red blood cells, myoglobin of muscle cells, and iron-containing enzymes. In the body, iron is stored as ferritin (a protein-iron complex) or hemosiderin. There are small amounts of ferritin found in blood circulation which is a good indicator of tissue ferritin stores. Tissue ferritin is found in all tissues but is concentrated within the liver, spleen, bone marrow, and skeletal muscles. Ferritin is stored intracellularly within lysosomes where it is degraded by the protein shells being stripped off and the iron is aggregated into hemosiderin granules. The surgical pathologist can analyze tissue iron concentrations by several methods, usually using an irone stain (Prussian blue or Perl's stain).
In the plasma, iron is transported by transferrin (a glycoprotein synthesized by the liver). Normally, about 1/3 of the transferrin is saturated by iron. Transferrin transfers iron to cells which utilize it for hemoglobin synthesis. Iron is absorbed from the gut (duodenum and to a lesser extent, the stomach, ileum, and colon) via two pathways. Iron that is derived from hemoglobin, myoglobin, and animal proteins is subjected to gastric acids which release it from the apoproteins and leave the heme. Heme is absorbed by the mucosal cells and degraded to release iron. Nonheme iron is absorped utilizing three proteins. Regulation of iron absorption is largely controlled by the rate of absorption which is closely tied to the total body iron content and erythropoietic activity. The HFew gene (HLA-H) may play a role in regulation.
PROTEIN ACTIONS Luminal mucins Bind iron at acid pH of stomach, keeping it soluble Integrin-like molecule In duodenum mucosal cells, iron is bound and transported across the cell membrane Mobilferrin Cytosolic protein accepts iron within the cell and delivers it to ferritin or transferrin Heme and nonheme iron within the cell cytoplasm is usually transferred to ferritin with a small amount transferred to serum transferrin.
OUTLINE
Reference Methods Clinical Utility Interfering Diseases or Substances that Alter Levels Commonly Used Terms Internet Links
CLINICAL UTILITY CHARACTERIZATION Iron Deficiency Dietary lack
Impaired absorption
Increased requirement
Chronic blood lossALOPECIA
- The diagnosis and treatment of iron deficiency and its potential relationship to hair loss.
Trost LB, Bergfeld WF, Calogeras E.
Department of Dermatology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Am Acad Dermatol. 2006 May;54(5):824-44. Abstract quote
Iron deficiency is the world's most common nutritional deficiency and is associated with developmental delay, impaired behavior, diminished intellectual performance, and decreased resistance to infection. In premenopausal women, the most common causes of iron deficiency anemia are menstrual blood loss and pregnancy. In men and postmenopausal women, the most common causes of iron deficiency anemia are gastrointestinal blood loss and malabsorption.
Hemoglobin concentration can be used to screen for iron deficiency, whereas serum ferritin concentration can be used to confirm iron deficiency. However, the serum ferritin concentration may be elevated in patients with infectious, inflammatory, and neoplastic conditions. Other tests may be needed, such as erythrocyte zinc protoporphyrin concentration, transferrin concentration, serum iron concentration, and transferrin saturation. The cause of iron deficiency must be identified. If the patient is male, postmenopausal female, or has risk factors for blood loss, then the patient should be evaluated for sources of blood loss, especially gastrointestinal (eg, colon cancer). Several studies have examined the relationship between iron deficiency and hair loss. Almost all have addressed women exclusively and have focused on noncicatricial hair loss. Some suggest that iron deficiency may be related to alopecia areata, androgenetic alopecia, telogen effluvium, and diffuse hair loss, while others do not.
Currently, there is insufficient evidence to recommend universal screening for iron deficiency in patients with hair loss. In addition, there is insufficient evidence to recommend giving iron supplementation therapy to patients with hair loss and iron deficiency in the absence of iron deficiency anemia. The decision to do either should be based on clinical judgment.
It is our practice at the Cleveland Clinic Foundation to screen male and female patients with both cicatricial and noncicatricial hair loss for iron deficiency. Although this practice is not evidence based per se, we believe that treatment for hair loss is enhanced when iron deficiency, with or without anemia, is treated. Iron deficiency anemia should be treated. Treating iron deficiency without anemia is controversial. Treatment of nutritional iron deficiency anemia includes adequate dietary intake and oral iron supplementation. Excessive iron supplementation can cause iron overload and should be avoided, especially in high-risk patients such as those with hereditary hemochromatosis. Patients who do not respond to iron replacement therapy should undergo additional testing to identify other underlying causes of iron deficiency anemia.
DISEASE SERUM IRON SERUM FERRI-TIN TRANS-FERRIN IRON SATU-RATION % TOTAL IRON BIND-ING CAPA-CITY TRANS-FERRIN SERUM TRANS-FERRIN RECEPTOR Hemochromatosis + + + - - Normal to low Iron deficiency anemia - - - + + High Sideroblastic anemia + + + - - Normal to high Thalassemia + + + - - High Porphyria cutanea tarda + + + - - Normal Anemia of chronic disease - + - - - Normal African siderosis + + + - - Normal to low
Laboratory Med 2001;9:506-508.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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Commonly Used Terms
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Last Updated May 9, 2006
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