Iron deficiency anemia is the most common type of anemia throughout the world. In the United States, iron deficiency anemia occurs to a lesser extent than in developing countries because of the higher consumption of red meat and the practice of food fortification (addition of iron to foods by manufacturers) (Fallon, 2013). Iron deficiency anemia can cause reduced work capacity in adults (Haas, 2001) and impact motor and mental development in children and adolescents (Halterman, 2001). The prevalence of iron deficiency anemia in the united states varies widely by age, sex, and race. This prevalence is known to be about 2 percent in adult men, 9 to 12 percent in non-Hispanic white women, and nearly 20 percent in black and Mexican-American women (Killip, 2007). There is some evidence that iron deficiency without anemia affects cognition in adolescent girls and causes fatigue in adult women. The Healthy People 2010 goals are to reduce the occurrence of iron deficiency anemia to less than 5 percent in toddlers, 1 percent in preschool-age children; and 7 percent in women of reproductive age, regardless of race (Healthy people 2010 ,2000).
Iron deﬁciency occurs in two main forms: absolute or functional. Absolute iron deﬁciency arises when total body iron stores are low or exhausted; functional iron deﬁciency is a disorder in which total body iron stores are normal or increased, but the iron supply to the bone marrow is inadequate. Absolute and functional deﬁciencies can coexist. Functional iron deﬁciency can be present in many acute and chronic inﬂammatory states (Bager, 2014).
Iron deficiency anemia results when iron demand by the body is not met by iron absorption from the diet (Killip, 2007). This occurs when the body does not have enough iron to produce a protein called hemoglobin. Hemoglobin is the part of red blood cells that gives blood its red color and enables the red blood cells to carry oxygenated blood throughout the body. If an individual is not consuming enough iron, or if losing too much iron, your body can’t produce enough hemoglobin, and iron deficiency anemia will eventually develop. It is also characterized by the production of red blood cells that are smaller than normal (microcytic) and appear pale or light colored (hypochromic) when viewed under a microscope. For this reason, the anemia that occurs with iron deficiency is also called hypochromic microcytic anemia (Fallon, 2013).
The normal range of hemoglobin is 12.0 to 15.5 grams per deciliter for an adult woman and 13.5 to 17.5 grams per deciliter for an adult man. In iron deficiency anemia, the hematocrit and hemoglobin levels are low. Iron absorption, which occurs mostly in the jejunum, is only 5 to 10 percent of dietary intake in persons in homeostasis. Iron metabolism is unusual in that it is controlled by absorption rather than excretion. Iron is only lost through blood loss or loss of cells as they slough (Killip, 2007).
Iron is an essential component of haemoglobin in red blood cells and of myoglobin in muscles, which contain around 60% of total body iron. It is also necessary for the functioning of various cellular mechanisms, including enzymatic processes, DNA synthesis, and mitochondrial energy generation. Because dietary intake is limited (1–2 mg per day), other sources are needed for iron homoeostasis e.g., recycling of ageing erythrocytes in macrophages, exchange of iron in iron-containing enzymes, and iron stores (Steinbicker, 2013). About 1–2 mg of iron is lost daily because of menstrual bleeding, sweating, skin desquamation, and urinary excretion (Steinbicker, 2013). Because iron does not have an excretion regulation pathway, dietary intake, intestinal absorption, and iron recycling should be ﬁnely regulated.
In iron deficiency anemia, your heart pumps more blood to make up for the low amount of oxygen. This could lead to irregular heartbeat. Severe iron deficiency can produce left ventricular dysfunction, an enlarged heart and overt heart failure (Ganz, 2003). Recently a high prevalence of Iron deficiency has been found in patients with Heart failure that also have a reduced ejection fraction (Heidenreich, 2013). Sustained iron deficiency has been shown in animal models to result in left ventricle hypertrophy and Left Ventricle dilatation, mitochondrial swelling, sarcomere disruption, and release of reactive oxygen species that can trigger cell injury (Zhang, 2005).
Inappropriate elevation of hepcidin (key regulator of the entry of iron into the circulation in mammals) is an important mechanism of anemia of chronic disease (Nanas, 2005). In inflammatory conditions, higher levels of hepcidin coincide with elevated inflammatory markers (IL6) and more severe disease (Weiss, 2005). In Heart failure, the opposite relationship has been demonstrated, with hepcidin levels found to be inversely related to the severity of disease. Current data suggest that those patients with Heart failure at highest risk of having concomitant Iron deficiency are women, non-Caucasian, older, anemic, and have more severe disease (Okonko, 2011). Depletion of myocardial iron stores has been demonstrated in patients with end-stage Heart failure referred for cardiac transplantation when compared with healthy hearts (Leszek, 2012).
Iron deficiency anemia, also leads to Increased heart rate to maintain greater cardiac output and Increased oxygen need of cardiac muscles due to increased work load. This all leads to the inability of your heart to meet demands during strenuous physical activity, and as the condition progresses, this will even occur when your body is at rest (Weiss, 2005). Anemia is found in as high as 50% of patients with heart failure. Anemia can worsen cardiac function and add further stress to the heart, which may lead to or worsen heart failure. Furthermore, anemia has also been associated with an increased risk of mortality. It is for these reasons that treating iron deficiency anemia is particularly important as it may reduce the risk of heart failure and related mortality (Weiss ,2005).
Chronic liver disease of any cause is frequently associated with hematological abnormalities. Among these, anemia is a frequent occurrence, seen in about 75% of patients with advanced liver disease. The etiology of anemia, especially in cirrhotic patients, is complex and multifactorial (Longo, 2006). The liver performs a major role in iron homeostasis. It is the main organ that produces the iron regulatory hormone hepcidin, expressed in iron excess conditions as well as in cases of inflammation, blocking the absorption of iron from the enterocytes (Manns, 2006).
Therefore, in Chronic liver disease, and especially in cases of severe hepatic injury, we expect to find low hepcidin levels. On the other hand, many chronic liver disease alcoholic and non-alcoholic liver disease, chronic hepatitis C virus infection are associated with a variable grade of iron overload that represents, together with inflammation, hepcidin production by the liver (Bosch, 2007). The production of hepcidin causes ferroprotein internalization, degradation and thus inhibition of iron export to the circulation. Hepcidin also inhibits divalent metal transporter-1 (DMT-1), blocking the absorption of iron in the duodenum. The production of hepcidin is inhibited by hypoxia, iron deficiency and erythroblastic activity, and triggered by inflammation and iron excess transferrin (Bosch, 2007).
One of the major, and potentially treatable, causes of anemia in patients with liver cirrhosis is acute or chronic blood loss into the gastrointestinal tract, often resulting in iron deficiency anemia. The hemorrhage is usually secondary to complications of portal hypertension such as gastroesophageal variceal rupture, gastropathy, gastric antral vascular ectasia or peptic ulcers, more common in patients with cirrhosis (Lozano, 2006). The fact that patients with liver disease have also had impaired coagulation is a contributing factor to the tendency of bleeding, as well as thrombocytopenia due to spleen enlargement. Acute hemorrhage is usually seen in variceal rupture or in a bleeding peptic ulcer (Abraldes, 2007). Chronic blood loss is mainly due to portal hypertensive gastropathy and gastric antral vascular ectasia. Both constitute lesions of the gastric mucosa caused by ectatic vessels in the stomach.
Iron deficiency anemia in Chronic kidney disease
Anemia is a common complication of chronic kidney disease, particularly in those with stage 3-5 disease and those on dialysis (MacDougall. 2010). The incidence of anemia increases as renal function deteriorates and erythropoiesis declines. (MacDougall. 2010) Erythropoiesis-stimulating agents, such as epoetin alfa, epoetin beta and darbepoetin alfa, are used to correct the anemia and avoid or reduce the need for red blood cell transfusions (Aljama, 2004). Erythropoiesis-stimulating agents therapy of anemia in patients with chronic kidney disease, recommend a target hemoglobin level generally in the range of 10-12 g/dL or 11-12 g/dL in adults to improve health related.
Anemia of chronic kidney disease, is one of the first signs of kidney dysfunction, yet it often goes undetected because of its insidious onset. Anemia develops gradually as kidney function declines and the glomerular filtration rate drops to 70 mL/min in male patients and 50 mL/min in females (Hsu, 2002). Epidemiologic data indicate that two-thirds of patients in the early stages of kidney failure are also anemic, with a hemoglobin level of less than 11 g/dL, yet only one-third of these patients have ever received erythropoietin-stimulating agents to treat their anemia (USRDS, 2009). The National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommend that the evaluation of anemia of chronic kidney disease, begin in patients with a serum creatinine ≥2 mg/dL when the hemoglobin is <12 g/dL in adult males and postmenopausal females and <11 g/dL in premenopausal females (KDOQ, 2007).
Many patients with chronic kidney disease, have iron deficiency anemia and are unable to produce adequate numbers of red blood cells. Iron deficiency can have many causes: not enough iron-rich food in the diet, chronic bleeding, malabsorption, or an occult gastrointestinal malignancy. Once iron deficiency anemia is diagnosed, a colonoscopy is warranted to rule out occult malignancy. Ferritin, a protein found mostly in macrophages and hepatocytes, stores iron and serves as a marker for total iron stores (Donnelly, 2001). Using stored iron requires transferrin, a transporting protein, to shuttle iron from the reticuloendothelial system and gut to the bone marrow. Chronic kidney disease, is a pro-inflammatory state that results in a limited ability to use iron stores. For this reason, patients with Chronic kidney disease require higher levels of iron (Weiner, 2005).
Patients with iron deﬁciency anemia can present with symptoms that are associated with all anemias. In addition to the most common like inability to concentrate, irritability and chronic fatigue, you should also be on guard for:
1. Very frequent: Paleness (45–50%), Fatigue (44%) Dyspnea and Headache (63%).
2. Frequent: Diﬀuse and moderate alopecia (30%), Atrophic glossitis (27%), Restless legs syndrome (24%), Dry and rough skin, Dry and damaged hair, Cardiac murmur (10%), Tachycardia (9%), Neurocognitive dysfunction, Angina pectoris and Vertigo.
3. Rare: Haemodynamic instability (2%), Syncope (03%), Koilonychia (spoon-shaped ﬁngernails) and Plummer-Vinson syndrome <01% (Novacek, 2010).
Clinical features of iron deﬁciency anemia depend on the severity of the anemia, age, comorbidities, chronicity and speed of onset. In some cases, anaemia is asymptomatic and diagnosed only after laboratory measurement of haemoglobin concentrations. Iron deﬁciency especially aﬀects epithelial cells with a rapid turnover, causing dryness and roughness of the skin, dry and damaged hair, diﬀuse and moderate alopecia, and koilonychia (spoon-shaped ﬁngernails) (Aydingoz, 1999).
The diagnosis of anaemia is made after conﬁrmation of a reduced blood haemoglobin concentration as shown by a full blood count. Thresholds to deﬁne anaemia depend on age, sex, pregnancy, altitude, and smoking. An adult man is deemed anemic when his haemoglobin concentration is less than 130 g/L, whereas an adult woman is judged anemic when her haemoglobin concentration is less than 120 g/L. In pregnancy, this cut oﬀ is lowered to 110 g/L (WHO, 2011).
The diagnosis of Iron deficiency anemia requires that a patient be anemic and show laboratory evidence of iron deficiency. Red blood cells in Iron deficiency anemia are usually described as being microcytic (i.e., mean corpuscular volume less than 80 µm3) and hypochromic, however the manifestation of iron deficiency occurs in several stages (Zanella, 1989). Patients with a serum ferritin concentration less than 25 ng per mL (25 mcg per L) have a very high probability of being iron deficient. The most accurate initial diagnostic test for Iron deficiency anemia is the serum ferritin measurement. Serum ferritin values greater than 100 ng per mL (100 mcg per L) indicate adequate iron stores and a low likelihood of Iron deficiency anemia (Guyatt ,1992).
In some populations, such as those with inflammatory disease or cirrhosis, these tests must be interpreted slightly differently because ferritin is an acute-phase reactant. Cutoffs for abnormality in these patients generally are higher (Israsena, 1998). Another laboratory change that occurs in patients with Iron deficiency anemia is an increase in the iron-carrying protein transferrin. The amount of iron available to bind to this molecule is reduced, causing a decrease in the transferrin saturation and an increase in the total iron-binding capacity. The serum transferrin receptor assay is a newer approach to measuring iron status at the cellular level. Increased levels are found in patients with Iron deficiency anemia, and normal levels are found in patients with anemia of chronic disease (Cook, 2003).
Physiological and pathological conditions can promote iron deﬁciency anemia. The maximum absorption of iron from the diet is less than the body’s requirements for iron, resulting in a risk of iron deﬁciency. In infants and young children aged 0–15 years, rapid growth consumes the iron stores that accumulate during gestation, which can, in turn, lead to an absolute deﬁciency (Dallman,1991). After childhood, adolescent girls are particularly at risk of iron deﬁciency anemia, because of menstrual iron losses (Harvey, 2005). During pregnancy, iron needs are tripled because of expansion of maternal red cell mass and growth of the fetus and placenta. Daily iron supplementation is signiﬁcantly associated with reduced risk of anemia at term (Cantor, 2015). Mothers who breastfeed are less likely to be iron deﬁcient than pregnant women because iron concentration in mature breastmilk is only 020–080 mg/L and most breastfeeders are amenorrhoeic. Regular blood donors are at increased risk of iron deﬁciency (Mozaheb ,2011).
Frequent blood donors who routinely donate blood may have an increased risk of iron deficiency anemia since blood donation can deplete iron stores (Cantor, 2015). Low hemoglobin related to blood donation may be a temporary problem remedied by eating more iron-rich foods. If you’re told that you can’t donate blood because of low hemoglobin, ask your doctor whether you should be concerned.
Treatment of Iron Deficiency Anemia
Transfusion should be considered for patients of any age with Iron deficiency anemia complaining of symptoms such as fatigue or dyspnea on exertion. It also should be considered for asymptomatic cardiac patients with hemoglobin less than 10 g per dL (100 g per L). However, oral iron therapy is usually the first-line therapy for patients with Iron deficiency anemia (Crosby, 1984).
Bone marrow response to iron is limited to 20 mg per day of elemental iron. An increase in the hemoglobin level of 1 g per dL (10 g per L) should occur every two to three weeks on iron therapy; however, it may take up to four months for the iron stores to return to normal after the hemoglobin has corrected (Fairbanks, 1991).
Ferrous sulfate in a dose of 325 mg provides 65 mg of elemental iron, whereas 325 mg of ferrous gluconate provides 38 mg of elemental iron. Sustained-release formulations of iron are not recommended as initial therapy because they reduce the amount of iron that is presented for absorption to the duodenal villi. Gastrointestinal absorption of elemental iron is enhanced in the presence of an acidic gastric environment. This can be accomplished through simultaneous intake of ascorbic acid i.e. vitamin C (Hallberg, 1986). Although iron absorption occurs more readily when taken on an empty stomach, this increases the likelihood of stomach upset because of iron therapy. Increased patient adherence should be weighed against the inferior absorption. Foods rich in tannates e.g. tea or phytates e.g. bran, cereal, or medications that raise the gastric pH e.g. antacids, proton pump inhibitors, histamine H2 blockers reduce absorption and should be avoided if possible (Sharma, 2004).
Some persons have difficulty absorbing the iron because of poor dissolution of the coating (Seligman, 1983). A liquid iron preparation would be a better choice for these patients. Laxatives, stool softeners, and adequate
Patient Education and Health Maintenance
- Educate patient on proper nutrition and good sources of iron; select well-balanced diet that includes animal proteins, iron-fortified cereals and bread, beans, dried fruits, legumes, tofu. The daily requirement of iron in adult females age 19 to 50 is 18 mg, for men 8mg; however, more is needed to build iron stores in those that have been anemic and for those who are at risk for anemia (Lippincott, 2014. P. 978).
- Teach patient about iron supplementation
A, Take iron on empty stomach with a full glass of water or fruit juice.
B, Liquid forms may stain teeth; mix well with water or fruit juice and use a straw.
C, Anticipate some epigastric discomforts, change in color of stools to green or black, and in some cases, nausea, constipation, or diarrhea. Prevent and treat constipation with increased fiber, fluids, and exercise. Report gastrointestinal intolerance to healthcare provider.
D, keep iron medications away from children as overdose may be fatal.
3. Encourage follow-up laboratory studies and visits to health care provider (Lippincott