IRON DEFICIENCY ANEMIA

IJEH LUCKY
OUTLINE

• INTRODUCTION
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• ETIOLOGY
• RISK FACTORS
• CLINICAL PRESENTATION
• STAGES
• MANAGEMENT
• DIFFERENTIAL DIAGNOSIS
• PREVENTION
• CONCLUSION
• REFERENCES
DIFFERENTIAL DIAGNOSIS CON'TD
 (eg, tetracycline). Ascorbic acid is the only common food
element known to increase nonheme iron absorption.
Iron Deficiency Anemia
PATHOPHYSIOLOGY BY PERMISSION OF THE PUBLISHER. FROM TEFFERI
A, LI C. IN ATLAS OF CLINICAL HEMATOLOGY .
EDITED BY JO ARMITAGE. PHILADELPHIA, CURRENT
• MEDICINE, 2004.
Iron is distributed in active metabolic and storage pools. Total body iron is about 3.5 g in healthy men and 2.5 g in women; the difference relates to women's smaller body size and dearth of stored iron because of iron loss due to menses. The distribution of
body iron is

• Hemoglobin: 2 g (men), 1.5 g (women) The average American diet, which contains 6 mg of
• Ferritin: 1 g (men), 0.6 g (women)
elemental iron/1000 kcal of food, is adequate for iron
• Hemosiderin: 300 mg

• Myoglobin: 200 mg
homeostasis. Of about 15 mg/day of dietary iron, adults
• Tissue enzymes (heme and nonheme): 150 mg absorb only 1 mg, which is the approximate amount lost
• Transport-iron compartment: 3 mg
daily by cell desquamation from the skin and intestines. In
• Iron absorption

•
iron depletion, absorption increases due to the
Iron is absorbed in the duodenum and upper jejunum. Absorption of iron is determined by the type of iron molecule and by what other substances are ingested. Iron absorption is best when food contains heme iron (meat). Dietary nonheme iron is usually in
the ferric state and must be reduced to the ferrous state and released from food binders by gastric secretions. Nonheme iron absorption is reduced by other food items (eg, vegetable fiber phytates and polyphenols; tea tannates, including phosphoproteins;
suppression of hepcidin, a key regulator of iron
bran) and certain antibiotics (eg, tetracycline). Ascorbic acid is the only common food element known to increase nonheme iron absorption.

• Iron Deficiency Anemia

•
metabolism; however, absorption rarely increases to > 6
BY PERMISSION OF THE PUBLISHER. FROM TEFFERI A, LI C. IN ATLAS OF CLINICAL HEMATOLOGY . EDITED BY JO ARMITAGE. PHILADELPHIA, CURRENT MEDICINE, 2004.

• mg/day unless supplemental iron is added (1). Children

The average American diet, which contains 6 mg of elemental iron/1000 kcal of food, is adequate for iron homeostasis. Of about 15 mg/day of dietary iron, adults absorb only 1 mg, which is the approximate amount lost daily by cell desquamation from the
skin and intestines. In iron depletion, absorption increases due to the suppression of hepcidin, a key regulator of iron metabolism; however, absorption rarely increases to > 6 mg/day unless supplemental iron is added (1). Children have a greater need for
iron and appear to absorb more to meet this need.

• Iron transport and usage

have a greater need for iron and appear to absorb more to
• meet this need.
Iron from intestinal mucosal cells is transferred to transferrin, an iron-transport protein synthesized in the liver; transferrin can transport iron from cells (intestinal, macrophages) to specific receptors on erythroblasts, placental cells, and liver cells. For heme
synthesis, transferrin transports iron to the erythroblast mitochondria, which insert the iron into protoporphyrin for it to become heme. Transferrin (plasma half-life, 8 days) is extruded for reutilization. Synthesis of transferrin increases with iron deficiency but
decreases with any type of chronic disease.

• Iron storage and recycling

Iron transport and usage
• Iron from intestinal mucosal cells is transferred to
Iron not used for erythropoiesis is transferred by transferrin, an iron-transporting protein, to the storage pool; iron is stored in 2 forms, ferritin and hemosiderin. The most important is ferritin (a heterogeneous group of proteins surrounding an iron core), which
is a soluble and active storage fraction located in the liver (in hepatocytes), bone marrow, and spleen (in macrophages); in RBCs; and in serum. Iron stored in ferritin is readily available for any body requirement. Circulating (serum) ferritin level parallels the
size of the body stores (1 ng/mL = 8 mg of iron in the storage pool). The 2nd storage pool of iron is in hemosiderin, which is relatively insoluble and is stored primarily in the liver (in Kupffer cells) and in bone marrow (in macrophages).

•
transferrin, an iron-transport protein synthesized in the
Because iron absorption is so limited, the body recycles and conserves iron. Transferrin grasps and recycles available iron from aging RBCs undergoing phagocytosis by mononuclear phagocytes. This mechanism provides about 97% of the daily iron
needed (about 25 mg of iron). With aging, iron stores tend to increase because iron elimination is slow
liver; transferrin can transport iron from cells (intestinal,
macrophages) to specific receptors on erythroblasts,
placental cells, and liver cells. For heme synthesis,
transferrin transports iron to the erythroblast mitochondria,
PATHOPHYSIOLOGY
• Iron is distributed in active metabolic and storage pools. Total body iron is about 3.5 g in healthy men and 2.5 g in women; the difference relates to women's smaller body size and dearth of stored iron because of iron loss due to menses. The distribution of
body iron is

• Hemoglobin: 2 g (men), 1.5 g (women)

• Ferritin: 1 g (men), 0.6 g (women)

• Hemosiderin: 300 mg

• Myoglobin: 200 mg

• Tissue enzymes (heme and nonheme): 150 mg

• Transport-iron compartment: 3 mg

• Iron absorption

• Iron is absorbed in the duodenum and upper jejunum. Absorption of iron is determined by the type of iron molecule and by what other substances are ingested. Iron absorption is best when food contains heme iron (meat). Dietary nonheme iron is usually in
the ferric state and must be reduced to the ferrous state and released from food binders by gastric secretions. Nonheme iron absorption is reduced by other food items (eg, vegetable fiber phytates and polyphenols; tea tannates, including phosphoproteins;
bran) and certain antibiotics (eg, tetracycline). Ascorbic acid is the only common food element known to increase nonheme iron absorption.

• Iron Deficiency Anemia

• BY PERMISSION OF THE PUBLISHER. FROM TEFFERI A, LI C. IN ATLAS OF CLINICAL HEMATOLOGY . EDITED BY JO ARMITAGE. PHILADELPHIA, CURRENT MEDICINE, 2004.

• The average American diet, which contains 6 mg of elemental iron/1000 kcal of food, is adequate for iron homeostasis. Of about 15 mg/day of dietary iron, adults absorb only 1 mg, which is the approximate amount lost daily by cell desquamation from the
skin and intestines. In iron depletion, absorption increases due to the suppression of hepcidin, a key regulator of iron metabolism; however, absorption rarely increases to > 6 mg/day unless supplemental iron is added (1). Children have a greater need for
iron and appear to absorb more to meet this need.

• Iron transport and usage

• Iron from intestinal mucosal cells is transferred to transferrin, an iron-transport protein synthesized in the liver; transferrin can transport iron from cells (intestinal, macrophages) to specific receptors on erythroblasts, placental cells, and liver cells. For heme
synthesis, transferrin transports iron to the erythroblast mitochondria, which insert the iron into protoporphyrin for it to become heme. Transferrin (plasma half-life, 8 days) is extruded for reutilization. Synthesis of transferrin increases with iron deficiency but
decreases with any type of chronic disease.

• Iron storage and recycling

• Iron not used for erythropoiesis is transferred by transferrin, an iron-transporting protein, to the storage pool; iron is stored in 2 forms, ferritin and hemosiderin. The most important is ferritin (a heterogeneous group of proteins surrounding an iron core), which
is a soluble and active storage fraction located in the liver (in hepatocytes), bone marrow, and spleen (in macrophages); in RBCs; and in serum. Iron stored in ferritin is readily available for any body requirement. Circulating (serum) ferritin level parallels the
size of the body stores (1 ng/mL = 8 mg of iron in the storage pool). The 2nd storage pool of iron is in hemosiderin, which is relatively insoluble and is stored primarily in the liver (in Kupffer cells) and in bone marrow (in macrophages).

• Because iron absorption is so limited, the body recycles and conserves iron. Transferrin grasps and recycles available iron from aging RBCs undergoing phagocytosis by mononuclear phagocytes. This mechanism provides about 97% of the daily iron
needed (about 25 mg of iron). With aging, iron stores tend to increase because iron elimination is slow
PATGOPHYSIOLOGY
• Iron is required for hemoglobin formation; if the supply is insufficient to produce normal
quantities of hemoglobin, the bone marrow ultimately is forced to produce cells that are
smaller than normal and poorly filled with hemoglobin. Iron is derived from the diet and
absorbed in the intestinal tract. Once in the body, it is retained and used over and over
again, only minimal amounts being lost through shedding of cells from the skin and the
exposed membranes and, in the female, through normal menstruation. In the adult the
body content is approximately 3.7 grams of iron, of which more than half is hemoglobin. In
the male there is virtually no further need for iron. Deficiency results if the dietary supplies
of iron are insufficient to meet the needs; if absorption is faulty, as in malabsorption
disorders; or if blood loss is occurring. Common causes of iron deficiency are excessive
menstrual loss in women and bleeding peptic ulcer in men. Iron deficiency is common in
infancy and childhood because demands are great for the ever-expanding pool of
circulating hemoglobin in the growing body, and in pregnancy when the fetus must be
supplied with iron. Hookworm infestation is a common cause of iron deficiency where
conditions for the worm are favourable, because the intestinal blood loss caused by
the myriad of worms attached to the wall is great.
• Persons with iron-deficiency anemiaare pale but not jaundiced. The deficiency of iron-
containing enzymes in the tissues, if sufficiently great, results in a smooth tongue; brittle,
flattened fingernails; and lustreless hair. Under the name of chlorosis
INTRODUCTION
The WHO defines anemia as hemoglobin <13 g/dL in men older
than age 15 years, <12 g/dL in nonpregnant women older than
age 15 years, and <11 g/dL in pregnant women. [1
] Iron deficiency is a lack of iron in the body resulting from
inadequate iron intake, increased iron loss, or excessive iron
requirements of which iron deficiency anemia (IDA) is the end-
stage result.
EPIDEMIOLOGY
• Iron-deficiency anemia affected about 1.48 billion people in
2015.[6] A lack of dietary iron is estimated to cause
approximately half of all anemia cases globally.[12]
• Women and young children are most commonly affected.[3] In
2015 anemia due to iron deficiency resulted in about 54,000
deaths – down from 213,000 deaths in 1990.[7][13]
• It is commoner in blacks, women in particular compared to any other
race.
ETIOLOGY
• Blood loss
• Hookworm infestation
• GI – oesophageal varies, hiatus hernia, peptic ulcer, aspirin ingestion,
gastric colonic & ceacal CA, hereditary telangiectasia, ulcerative
colitis, angiodysplasia, haemorrhoids, meckel’s diverticulum
• ĺUterine – menorrhagia, postmenopausal bleeding, prolonged
bleeding during parturition
• Pulmonary – haemoptysis, pulmonary idiopathic haemosiderosis,
Goodpasture syndro
ETIOLOGY
• Renal tracts – haematuria( renal/bladder lesion), haemoglobinuria(PNH,
cardiac valve prosthesis)Widespread bleeding disorders
• Increased demands – infants, children, adolescents, pregnant & lactating
women
• Inadequate iron supply
• Poor nutritional intake in children
• malabsorption – gastrectomy, Gluten-induced enteropathy, crohn’s disease,
coeliac sprue, atrophic gastritis, achlorhydria
• Abnormal atransferrinaemia function – congenital atransferrinaemia,
autoantibodies to transferrin receptors
RISK FACTOR
• These groups of people may have an increased risk of iron deficiency anemia:
• Women who menstruate, particularly if menstrual periods are heavy
• Women who are pregnant or breastfeeding or those who have recently given birth
• People who have undergone major surgery or physical trauma
• People with gastrointestinal diseases such as celiac disease (sprue), inflammatory
bowel diseases such as ulcerative colitis, or Crohn disease
• People with peptic ulcer disease
• People who have undergone bariatric procedures, especially gastric bypass
operations
• Vegetarians, vegans, and other people whose diets do not include iron-rich foods
(Iron from vegetables, even those that are iron-rich, is not absorbed as well as
iron from meat, poultry, and fish.)
• Children who drink more than 16 to 24 ounces a day of cow's milk (Cow's milk
not only contains little iron, but it can also decrease absorption of iron and
irritate the intestinal lining causing chronic blood loss.)
CLINICAL PRESENTATION
• Symptoms of iron-deficiency anemia are related to decreased oxygen
delivery to the entire body and may include:
• Being pale or having yellow "sallow" skin
• Unexplained fatigue or lack of energy
• Shortness of breath or chest pain, especially with activity
• Unexplained generalized weakness
• Rapid heartbeat
• Pounding or "whooshing" in the ears
• Headache, especially with activity
• Craving for ice or clay - "picophagia"
• Sore or smooth tongue
• Brittle nails or hair loss
INVESTIGATIONS
• Iron-deficiency anemia is diagnosed by blood tests that should include
a complete blood count (CBC). Additional tests may be ordered to
evaluate the levels of serum ferritin, iron, total iron-binding capacity,
and/or transferrin. In an individual who is anemic from iron deficiency,
these tests usually show the following results:
• Low hemoglobin (Hg) and hematocrit (Hct)
• Low mean cellular volume (MCV)
• Low ferritin
• Low serum iron (FE)
• High transferrin or total iron-binding capacity (TIBC)
• Low iron saturation
• The peripheral smear or blood slide may show small, oval-shaped cells
with pale centers. In severe iron deficiency, the white blood count
(WBC) may be low and the platelet count may be high or low.
INVESTIGATION CON’TD
• Red blood cell size and color. With iron deficiency anemia, red
blood cells are smaller and paler in color than normal.
• Hematocrit. This is the percentage of your blood volume made up
by red blood cells. Normal levels are generally between 34.9 and
44.5 percent for adult women and 38.8 to 50 percent for adult men.
These values may change depending on your age.
• Hemoglobin. Lower than normal hemoglobin levels indicate anemia.
The normal hemoglobin range is generally defined as 13.5 to 17.5
grams (g) of hemoglobin per deciliter (dL) of blood for men and 12.0
to 15.5 g/dL for women. The normal ranges for children vary
depending on the child's age and sex.
• Ferritin. This protein helps store iron in your body, and a low level of
ferritin usually indicates a low level of stored iron.
INVESTIGATION CON’TD
• If your bloodwork indicates iron deficiency anemia, your doctor may order
additional tests to identify an underlying cause, such as:
• Endoscopy. Doctors often check for bleeding from a hiatal hernia, an ulcer or the
stomach with the aid of endoscopy. In this procedure, a thin, lighted tube
equipped with a video camera is passed down your throat to your stomach. This
allows your doctor to view the tube that runs from your mouth to your stomach
(esophagus) and your stomach to look for sources of bleeding.
• Colonoscopy. To rule out lower intestinal sources of bleeding, your doctor may
recommend a procedure called a colonoscopy. A thin, flexible tube equipped with
a video camera is inserted into the rectum and guided to your colon. You're
usually sedated during this test. A colonoscopy allows your doctor to view inside
some or all of your colon and rectum to look for internal bleeding.
• Ultrasound. Women may also have a pelvic ultrasound to look for the cause of
excess menstrual bleeding, such as uterine fibroids.
DIFFERENTIAL DIAGNOSIS
• The presence of anaemia with micro cytosis and hypochromia does
not necessarily indicate iron deficiency.
• The most common other causes are thalassemia, sideroblastic
anaemia and anaemia of chronic disease, and in these disorders the
iron stores are normal or increased.
ETIOLOGY
• Parasitic diseaseEdit
• The leading cause of iron-deficiency anemia worldwide is a parasitic
disease known as a helminthiasis caused by infestation with
parasitic worms (helminths); specifically, hookworms. The
hookworms most commonly responsible for causing iron-deficiency
anemia include Ancylostoma duodenale, Ancylostoma ceylanicum,
and Necator americanus.[22][25] The World Health
Organization estimates that approximately two billion people are
infected with soil-transmitted helminths worldwide.[26] Parasitic
worms cause both inflammation and chronic blood loss by binding to
a human's small-intestinal mucosa, and through their means of
feeding and degradation, they can ultimately cause iron-deficiency
anemia.[16][25]
MANAGEMENT
• The diagnosis of iron deficiency anaemia relies on a clinical history
which should include questions about
• dietary intake,
• self-medication with non-steroidal anti-inflammatory drugs ( which
may give rise to gastrointestinal bleeding), and the
• presence of blood in the faeces ( which may be a sign of Ha
emorrhoids or carcinoma of the lower bowel).
• In women, a careful enquiry about the duration of periods, the
occurrence if clots and the number of sanitary towels or tampons(
normal 3-5/day) used should be made.
CONCLUSION
MANAGEMENT
• Aim is to restore the heamoglobin concentration, red cell indices and
to replenish the iron stores
• Treatment of underlying cause will prevent further iron loss but all
patients should have iron supplementation to achieve above aim
• Oral iron therapy is usually adequate to restore iron stores in most
patients; it is efficient, well tolerated & cost effective
• It is well absorbed with few side effects (heartburn, abdominal pain,
nausea, diarrhoea & constipation)
STAGES OF IRON DEFICIENCY
• Laboratory test results help stage iron deficiency anemia.
• Stage 1 is characterized by decreased bone marrow iron stores;
hemoglobin (Hb) and serum iron remain normal, but the serum ferritin level
falls to < 20 ng/mL. The compensatory increase in iron absorption causes
an increase in iron-binding capacity (transferrin level).
• During stage 2, erythropoiesis is impaired. Although the transferrin level is
increased, the serum iron level decreases; transferrin saturation
decreases. Erythropoiesis is impaired when serum iron falls to < 50 μg/dL
(< 9 μmol/L) and transferrin saturation to < 16%. The serum transferrin
receptor level rises (> 8.5 mg/L).
• During stage 3, anemia with normal-appearing RBCs and indices
develops.
• During stage 4, microcytosis and then hypochromia develop.
• During stage 5, iron deficiency affects tissues, resulting in symptoms and
signs.
STAGES OF IRON DEFICIENCY
• Iron deficiency develops in stages. In the first stage, iron
requirement exceeds intake, causing progressive depletion of
bone marrow iron stores. As stores decrease, absorption of
dietary iron increases in compensation. During later stages,
deficiency impairs RBC synthesis, ultimately causing anemia.
• Severe and prolonged iron deficiency also may cause
dysfunction of iron-containing cellular enzymes.
PREVENTION
• You can reduce your risk of iron deficiency anemia by choosing iron-rich foods.
• Choose iron-rich foods
• Foods rich in iron include:
• Red meat, pork and poultry
• Seafood
• Beans
• Dark green leafy vegetables, such as spinach
• Dried fruit, such as raisins and apricots
• Iron-fortified cereals, breads and pastas
• Peas
• Your body absorbs more iron from meat than it does from other sources. If you choose to
not eat meat, you may need to increase your intake of iron-rich, plant-based foods to
absorb the same amount of iron as does someone who eats meat.
PREVENTION
• Choose foods containing vitamin C to enhance iron absorption
• You can enhance your body's absorption of iron by drinking citrus juice or eating other foods rich in vitamin C at the
same time that you eat high-iron foods. Vitamin C in citrus juices, like orange juice, helps your body to better absorb
dietary iron.
• Vitamin C is also found in:
• Broccoli
• Grapefruit
• Kiwi
• Leafy greens
• Melons
• Oranges
• Peppers
• Strawberries
• Tangerines
• Tomatoes
PREVENTION
• To prevent iron deficiency anemia in infants, feed your baby
breast milk or iron-fortified formula for the first year. Cow's milk
isn't a good source of iron for babies and isn't recommended for
infants under 1 year. After age 6 months, start feeding your
baby iron-fortified cereals or pureed meats at least twice a day
to boost iron intake. After one year, be sure children don't drink
more than 20 ounces (591 milliliters) of milk a day. Too much
milk often takes the place of other foods, including those that
are rich in iron.
MANAGEMENT CON'TD
• When iron complexes or chelated forms (carboxylated inulin-iron
complex/thiolated inulin-iron complex) are used, GI symptoms are
minimal and these contain ferric chloride which is more bioavailable
• Sustained slow release / enteric coated iron should not be used as
much of the iron is carried past the duodenum to the sites of poor
absorption.
MANAGEMENT CON'TD
• Give for 3-6months to restore iron stores & red cell haemoglobin fully
but by 1 month increase in haemoglobin is apparentRate of response
:1.5-2.0g/L/day or 20g/L every 3weeks rise in haemoglobin
• Ascorbic acid may be given to enhance absorption
• Failure to respond to oral iron
• Poor compliance
• Continuous haemorrhage
• malabsorption
MANAGEMENT CON'TD
• Wrong diagnosis
• Renal & liver failure
• Mixed deficiency – folate & B12
• Malignancy & infection (H. pylori, chronic gastritis)
• Use of slow release preparation
• Parenteral therapy is necessary for patientsIntolerant or unresponsive to
oral iron supplement
• Receiving EPO
• Severe IDA diagnosed in late pregnancy
• Chronic dialysis
MANAGEMENT CON'TD
• Parenteral iron is best given IV because IM iron has been associated
with development of soft-tissue sarcomas
• Types of parenteral iron preparations
• Iron dextran – is cheap & has ability to give total iron replacement of
≥ 2g with single infusion, although it comes in 2ml(100mg) aliquots. It
can cause anaphylactic reaction in <1% of cases. Thus, test dose of
0.5ml(25mg) should be given prior to infusion
MANAGEMENT CON'TD
• The deficit should be calculated from the degree of anaemia,is usually
1-2g
• Iron(mg) = Hb deficit (target-actual Hb)mg/dl X weight(Ibs) + iron
store
• In patient receiving erythropoietin treatment in CRF, smaller IV doses
25-125mg/week may be used, with regular monitoring of serum
ferritin to prevent iron overload
• Iron sucrose and sorbitol – are associated with lower incidence of
anaphylaxis, and no fatal cases have been reported. They are however
expensive and total replacement can not be given with single infusion
MANAGEMENT CON'TD
• Iron sorbitol is given deep IM 50-100mg/day while iron sucrose is
given by slow IV infusion or injection
• From all parenteral preparation, iron complex is taken up
macrophages of the RES, from which iron is released to circulating
transferrin which carries it to the BM. 4 -7 days following therapy,
response is seen with reticulocytosis. Normalization of reticulocyte
haemoglobin content is the early indicator of response & Hb response
is about 1-2 weeks but full response takes several weeks