Approach to a case of Iron Defciency Anaemia

Investigatory approach for interlinking among Iron deficiency Anemia , IDD & Fluorosis

Anaemia: Definition of anaemia and prevalence of IDDAnaemia is defined as a reduction of the haemoglobin concentration, red-cell count, or packed cell volume to below normal levels.Some 2 billion people worldwide are affected by iron-deficiency anaemia (IDD).

IDD is widely prevalent in India, with 20% of adult males, 40% of children and adult non-pregnant females80% of pregnant females being affected.

Classification

The main groups of anaemias classified according to the underlying causeReduced red-cell production: Defective precursor proliferation Defective precursor maturation Defective proliferation and maturation Increased rate of red-cell destruction: Haemolysis Loss of red cells from the circulation: Bleeding

Distribution and loss of iron

1.The total amount of iron in the adult body is between 3 and 4 gm as haem 2. Haem is found as haemoglobin and myoglobin, although appreciable quantities are found the liver, kidney and intestine

3. In a normal individual, the average red cell life span is 120 days. Thus, 0.81% of red cells turn over each day. Because each milliliter of red cells contains 1 mg of elemental iron, the amount of iron needed to replace those red cells lost through senescence amounts to 20 mg/d (assuming an adult with a red cell mass of 2 L

Adult male 80 kg (mg)Adult female 60 kg (mg)Haemoglobin25001700Myoglobin/ enzymes500300Transferrin iron33Stores600 to 10000 to 300

Recommended daily allowance for iron.Current recommended dietary allowances of iron forIndians:Boy 16-18yrs 50 (mg of iron/day)Girl 16-18 30Men >18 28 Women >18 30Pregnant women 38

*Computed based on absorption rates of 3 per cent for males,5 percent for females

Causes of iron deficiency

Increased Demand for IronRapid growth in infancy or adolescencePregnancyErythropoietin therapyIncreased Iron LossChronic blood lossMensesAcute blood lossBlood donationPhlebotomy as treatment for polycythemia veraDecreased Iron Intake or AbsorptionInadequate dietMalabsorption from disease (sprue, Crohn's disease)Malabsorption from surgery (postgastrectomy)Acute or chronic inflammation

Absorption of iron from gut and homeostasisIron absorptionthis occurs in the duodenum and upper jejunum and the following complex processes are involved: (1) divalent metal transporter protein (DMT1)essential for uptake of ferrous ions by gut cells and erythron(2) ferrireductasereduces ferric form to ferrous (3) uptake of haem by enterocytesmediated by an unknown membrane protein; (4) ferroportinmediates egress of ferric ions from enterocytes.

Iron homeostasisthis is maintained by rigorous control of absorption from the diet orchestrated by the peptide hormone, hepcidin, which is synthesized by the liver and regulates the process by inhibiting efflux of iron from enterocytes.

Iron metabolism and Haem synthesis Most body iron is present in haemoglobin in circulating red cellsThe macrophages of the reticuloendotelial system store iron released from haemoglobin as ferritin and haemosiderinThey 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 haemoglobinThere 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.

Iron cycle

FeFe

FeFeFe

FerritinHemosiderin

slow

FeFe

FeFe

FeFeFe

Fe

Fe

FerritinFerritinTransferrin Receptor

RBC PRECURSOR

CIRCULATING RBCs

FeFeTRANSFERRIN

MONONUCLEARPHAGOCYTES

Stages in the development of iron deficiency*Prelatent :- the stage of negative iron balancereduction in iron stores without reduced serum iron levels

Latent:- stage of iron-deficient erythropoiesisiron stores are exhausted, but the blood haemoglobin level remains normal

Stage of Iron deficiency anemiablood haemoglobin concentration falls below the lower limit of normal

*discussed in detail later

Approach to IDD will be considered under the following heads:HistoryClinical features: general and specificExaminationBlood testsBone marrow pictureDifferential diagnosisTreatment

History

In slowly developing anaemia, even at very low haemoglobin levels, symptoms of anaemia may be absent.

History of a sore tongue, dysphagia, dyspepsia, bleeding from any site, and of symptoms suggestive of malabsorption is important in cases of anaemia.

Family history is important mainly in haemolytic anaemias eg. thalassaemias in Sindhis, KutchhisSickle cell disease in PatelsG-6-PD deficiency in Parsis

Symptoms of anaemias in generalCan be classified as per each system:

FatigueDizziness, light headednessHeadacheInsomniaTinnitusPalpitationDyspnoeaLethargyDisturbances in menstruation, reduced libidoImpaired growth in infancy

Symptoms of IDD IrritabilityPoor attention span with lack of interest in surroundingsPoor work performanceBehavioural disturbancesPica (geophagia. pagophagia, abnormal food cravings)Defective structure and function of epithelial tissue especially affected are the hair, the skin, the nails, the tongue, the mouth, the hypopharynx and the stomachIncreased frequency of infection.

Pica (perverted eating habits)The habitual ingestion of unusual substancesearth, clay (geophagia)laundry starch (amylophagia)ice (pagophagia)

Usually is a manifestation of iron deficiency and is relieved when the deficiency is treatedIt is dangerous because it can lead to helmenthiasis (hookworm)

Abnormalities in physical examinationPallor - of skin, lips, nail beds and conjunctival mucosaNails - flattened, fragile, brittle, -koilonychia( hollow nail) due to retarded growth of nail plate. 3 stages: brittleness, platynychia and spooningTongue and mouthAtrophic glossitis, angular cheiliosis, stomatitisDysphagia

Stomachatrophic gastritis, (reduction in gastric secretion, malabsorption)

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

KOILONYCHIA

&

ATROPHIC GLOSSITIS

Angular cheiliosis

Laboratory investigationsThe single most important investigation is a careful examination of a good-quality Romanowsky-stained peripheral smear (PS).Some common morphologic abnormalities of the red cells seen on PBS in IDD are as follows :

AbnormalitySignificance Hypochromia (Defective haemoglobinisation) iron-deficiency anaemia, thalassaemias Microcytosis (Defective haemoglobinisation) iron-deficiency anaemia, thalassaemias Anisocytosis (Variation in size of cells) iron-deficiency anaemia, thalassaemias haemoglobinopathies

Pencil cells and target cells are amongst others to be seen and both are theresult of defective haemoglobinisation and/or excess membrane

Normocytic Normochromic and Microcytic Hypochromic PBS: A compraison

Pencil cells: Oval to elongated, ellipsoid shape with central area of pallor and hemoglobin at both ends of cell

Significance: Iron deficiency anaemia (Elongated cells) Vitamin B12 deficiency anaemia (Oval Cells)

Anisocytosis RBC show abnormal size variation Significance: Iron deficiency Vit B12 deficiency

Target Cells:

Characterised by thin bulls-eye shape and an increase in the surface membrane area to volume ratio due to a decrease in Hb

Significance: Iron Deficiency Anaemia, Vit B12 deficiency Anaemia and other disorders (eg Liver Disorders, Thalassemia)

Reticulocyte count: (N= upto 2%)This gives an estimate of the adequacy of the marrow response to the anaemia. Reticulocytes are young red cells with presence of nuclear remnants in the cytoplasmReticulocytopenia occurs in nutritional deficiency anaemias and aplastic anaemia

Laboratory findings (1)Blood testserythrocyteshemoglobin level packed cell volume (PCV) RBCMCV and MCH Retic count anisocytosispoikilocytosisHypochromia

leukocytes normalplateletsusually normal or thrombocytosis

Iron studiesSerum Iron - the amount of circulating iron bound to transferrin(normal range is 50150 g/dL)Total Iron-Binding Capacity(TIBC) - an indirect measure of the circulating transferrin (normal range is 300360 g/dL)the serum ferritin level correlates with total body iron stores; thus, is the most convenient laboratory test to estimate iron stores. The normal value for ferritin in Adult males 100 g/L, while adult females 30 g/L.Red cell protoporphyrin : reflects an inadequate iron supply to erythroid precursors to support hemoglobin synthesis. Normal values are