Iron Deficiency

Disorders of iron metabolism and hem synthesis • Iron deficiency and iron deficiency anemia • The anemia of chronic disorders • Sideroblastic anemias • Methemoglobinemia and other disorders with cyanosis • Hemochromatosis • Porphyria

Iron metabolism • Most body iron is present in haemoglobin in circulating red cells • The macrophages of the reticuloendotelial system store iron released from haemoglobin as ferritin and haemosiderin • They release iron to plasma, where it attaches to transferrin which takes it to tissues with transferrin receptors – especially the bone marrow – where the iron is incorporated by erythroid cells into haemoglobin • There is a small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily) is replaced by iron absorbed from the diet.

Stages in the development of iron deficiency • Prelatent – reduction in iron stores without reduced serum iron levels • Hb (N), MCV (N), iron absorption (↑), transferin saturation (N), serum ferritin (↓), marrow iron (↓)

• Latent – iron stores are exhausted, but the blood haemoglobin level remains normal • Hb (N), MCV (N), TIBC (↑), serum ferritin (↓), transferin saturation (↓), marrow iron (absent)

• Iron deficiency anemia – blood haemoglobin concentration falls below the lower limit of normal • Hb (↓), MCV (↓), TIBC (↑), serum ferritin (↓), transferin saturation (↓), marrow iron (absent)

Iron deficiency and iron deficiency anemia • The characteristic sequence of events ensues when the total body iron level begins to fall: 1. decreases the iron stores in the macrophages of the liver, spleen and bone marrow 2. increases the amount of free erythrocyte protoporphiryn (FEP) 3. begins the production of microcytic erythrocytes 4. decreases the blood haemoglobin concentration

Iron deficiency anemia Definition and etiologic factors • The end result of a long period of negative iron balance – decreased iron intake • inadequate diet, impaired absorption, gastric surgery, celiac disease

– increased iron loss • gastrointestinal bleeding (haemorrhoids, salicylate ingestion, peptic ulcer, neoplasm, ulcerative colitis) • excessive menstrual flow, blood donation, disorders of hemostasis

– increased physiologic requirements for iron • infancy, pregnancy, lactation

– cause unknown (idiopathic hypochromic anemia)

Iron deficiency anemia Clinical manifestation • Presentation of – underlying disease

37%

– anemia symptoms

63%

Symptoms of anemia

• • • • • • • •

Fatigue Dizziness Headache Palpitation Dyspnea Lethargy Disturbances in menstruation Impaired growth in infancy

Symptoms of iron deficiency • • • • • • •

Irritability Poor attention span Lack interest in surroundings Poor work performance Behavioural disturbances Pica Defective structure and function of epithelial tissue – especially affected are the hair, the skin, the nails, the tongue, the mouth, the hypopharynx and the stomach

• Increased frequency of infection

Pica • The habitual ingestion of unusual substances – earth, clay (geophagia) – laundry starch (amylophagia) – ice (pagophagia)

• Usually is a manifestation of iron deficiency and is relieved when the deficiency is treated

Abnormalities in physical examination • Pallor of skin, lips, nail beds and conjunctival mucosa • Nails - flattened, fragile, brittle, koilonychia, spoon-shaped • Tongue and mouth – glossitis, angular cheliosis, stomatitis – dysphagia (Peterson-Kelly or Plummer-Vinson syndrome (carcinoma in situ)

• Stomach – atrophic gastritis, (reduction in gastric secretion, malabsorbtion)

• The cause of these changes in iron deficiency is uncertain, but may be related to the iron requirement of many enzymes present in epithelial and other cells

Laboratory findings (1) • Blood tests – erythrocytes • • • • • • •

hemoglobin level the volume of packed red cells (VPRC) RBC MCV and MCH anisocytosis poikilocytosis hypochromia

– leukocytes • normal

– platelets • usually thrombocytosis

↓ ↓ ↓ ↓

Laboratory findings (2) • Iron metabolism tests – – – – – – –

serum iron concentration total iron-binding capacity saturation of transferrin serum ferritin levels sideroblasts serum transferrin receptors FEP

↓ ↑ ↓ ↓ ↓ ↑ ↑

Laboratory findings (3) • Bone marrow test – high cellularity – mild to moderate erythroid hyperplasia (25-35%; N 16 – 18%) – the cytoplasm of polychromatic and pyknotic erythroblasts is scanty, vacuolated and irregular in outline. This type of erythropoiesis has been described as micronormoblastic – bone marrow showing absence of stainable iron

Management of iron deficiency anemia • Correction of the iron deficiency – orally – intramuscularly – intravenously

• Treatment of the underlying disease

Oral iron therapy • The optimal daily dose - 200 mg of elemental iron –Ferrous •Gluconate •Fumarate •sulphate

5 tablets/day 3 tablets/day 3 tablets/day

– iron is absorbed more completely when the stomach is empty – it is necessary to continue treatment for 3 - 6 months after the anemia is relived – iron absorption » is enhanced: vitC, meat, orange juice, fish » is inhibited: cereals, tea, milk

•side effects – heartburn, nausea, abdominal cramps, diarrhoea

Failure of oral iron therapy • Incorrect diagnosis • Complicating illness • Failure of the patient to take prescribed medication • Inadequate prescription (dose or form) • Continuing iron loss in excess of intake • Malabsorbtion of iron

Parenteral iron therapy (1) • Is indicated when the patient – demonstrated intolerance to oral iron – loses iron (blood) at a rate to rapid for the oral intake – has a disorder of gastrointestinal tract – is unable to absorb iron from gastrointestinal tract

Parenteral iron therapy (2) • Preparations and administration – iron - dextran complex (50mg iron /ml) • intramuscularly or intravenously • necessary is the test for hypersensitivity • the maximal recommended daily dose - 100mg (2ml) – total dose is calculated from the amount of iron needed to restore the haemoglobin deficit and to replenish stores • iron to be injected (mg) = (15-pts Hb/g%/) x body weight (kg) x 3

Parenteral iron therapy (3) • Side effects • local: pain at the injection site, discoloration of the skin, lymph nodes become tender for several weeks, pain in the vein injected, flushing, metallic taste • systemic: – immediate: hypotension, headache, malaise, urticaria, nausea, anphylactoid reactions – delayed: lymphadenophaty, myalgia, artralgia, fever